StemCell Therapy

Ophthalmology ( or )[1] is the branch of medicine that deals with the anatomy, physiology and diseases of the eye.[2] An ophthalmologist is a specialist in medical and surgical eye problems. Since ophthalmologists perform operations on eyes, they are both surgical and medical specialists. A multitude of diseases and conditions can be diagnosed from the eye.[3]

The Greek roots of the word ophthalmology are (ophthalmos, "eye") and -o (-logia, "study, discourse"),[4][5] i.e., "the study of eyes". The discipline applies to all animal eyes, whether human or not, since the practice and procedures are quite similar with respect to disease processes, while differences in anatomy or disease prevalence, whether subtle or substantial, may differentiate the two.[citation needed]

The Indian surgeon Sushruta wrote Sushruta Samhita in Sanskrit in about 800 BC which describes 76 ocular diseases (of these 51 surgical) as well as several ophthalmological surgical instruments and techniques.[6][7] His description of cataract surgery was more akin to extracapsular lens extraction than to couching.[8] He has been described as the first cataract surgeon.[9][10]

The pre-Hippocratics largely based their anatomical conceptions of the eye on speculation, rather than empiricism.[11] They recognized the sclera and transparent cornea running flushly as the outer coating of the eye, with an inner layer with pupil, and a fluid at the centre. It was believed, by Alcamaeon and others, that this fluid was the medium of vision and flowed from the eye to the brain by a tube. Aristotle advanced such ideas with empiricism. He dissected the eyes of animals, and discovering three layers (not two), found that the fluid was of a constant consistency with the lens forming (or congealing) after death, and the surrounding layers were seen to be juxtaposed. He and his contemporaries further put forth the existence of three tubes leading from the eye, not one. One tube from each eye met within the skull.

Rufus of Ephesus recognised a more modern eye, with conjunctiva, extending as a fourth epithelial layer over the eye.[12] Rufus was the first to recognise a two-chambered eye, with one chamber from cornea to lens (filled with water), the other from lens to retina (filled with an egg white-like substance). The Greek physician Galen remedied some mistakes including the curvature of the cornea and lens, the nature of the optic nerve, and the existence of a posterior chamber.

Though this model was a roughly correct modern model of the eye, it contained errors. Still, it was not advanced upon again until after Vesalius. A ciliary body was then discovered and the sclera, retina, choroid, and cornea were seen to meet at the same point. The two chambers were seen to hold the same fluid, as well as the lens being attached to the choroid. Galen continued the notion of a central canal, but he dissected the optic nerve and saw that it was solid. He mistakenly counted seven optical muscles, one too many. He also knew of the tear ducts.

Medieval Islamic Arabic and Persian scientists (unlike their classical predecessors) considered it normal to combine theory and practice, including the crafting of precise instruments, and therefore found it natural to combine the study of the eye with the practical application of that knowledge.[13] Hunain ibn Ishaq, and others beginning with the medieval Arabic period, taught that the crystalline lens is in the exact center of the eye.[14] This idea was propagated until the end of the 1500s.[14]

Ibn al-Haytham (Alhazen), an Arab scientist with Islamic beliefs, wrote extensively on optics and the anatomy of the eye in his Book of Optics (1021).

Ibn al-Nafis, an Arabic native of Damascus, wrote a large textbook, The Polished Book on Experimental Ophthalmology, divided into two parts, On the Theory of Ophthalmology and Simple and Compounded Ophthalmic Drugs.[15]

In the 17th and 18th centuries, hand lenses were used by Malpighi, and microscopes by van Leeuwenhoek, preparations for fixing the eye for study by Ruysch, and later the freezing of the eye by Petit. This allowed for detailed study of the eye and an advanced model. Some mistakes persisted, such as: why the pupil changed size (seen to be vessels of the iris filling with blood), the existence of the posterior chamber, and of course the nature of the retina. In 1722, van Leeuwenhoek noted the existence of rods and cones,[citation needed] though they were not properly discovered until Gottfried Reinhold Treviranus in 1834 by use of a microscope.

Georg Joseph Beer (17631821) was an Austrian ophthalmologist and leader of the First Viennese School of Medicine. He introduced a flap operation for treatment of cataracts (Beer's operation), as well as popularizing the instrument used to perform the surgery (Beer's knife).[16]

The first ophthalmic surgeon in Great Britain was John Freke, appointed to the position by the Governors of St Bartholomew's Hospital in 1727. A major breakthrough came with the appointment of Baron Michael Johann Baptist de Wenzel (172490), a German who became oculist to King George III of England in 1772. His skill at removing cataracts legitimized the field.[17] The first dedicated ophthalmic hospital opened in 1805 in London; it is now called Moorfields Eye Hospital. Clinical developments at Moorfields and the founding of the Institute of Ophthalmology (now part of the University College London) by Sir Stewart Duke Elder established the site as the largest eye hospital in the world and a nexus for ophthalmic research.[18]

The prominent opticians of the late 19th and early 20th centuries included Ernst Abbe (18401905), a co-owner of at the Zeiss Jena factories in Germany where he developed numerous optical instruments. Hermann von Helmholtz (1821-1894) was a polymath who made contributions to many fields of science and invented the ophthalmoscope in 1851. They both made theoretical calculations on image formation in optical systems and had also studied the optics of the eye.

Numerous ophthalmologists fled Germany after 1933 as the Nazis began to persecute those of Jewish descent. A representative leader was Joseph Igersheimer (18791965), best known for his discoveries with arsphenamine for the treatment of syphilis. He fled to Turkey in 1933. As one of eight emigrant directors in the Faculty of Medicine at the University of Istanbul, he built a modern clinic and trained students. In 1939, he went to the United States, becoming a professor at Tufts University.[19]

Polish ophthalmology dates to the 13th century. The Polish Ophthalmological Society was founded in 1911. A representative leader was Adam Zamenhof (18881940), who introduced certain diagnostic, surgical, and nonsurgical eye-care procedures and was shot by the Nazis in 1940.[20] Zofia Falkowska (191593) head of the Faculty and Clinic of Ophthalmology in Warsaw from 1963 to 1976, was the first to use lasers in her practice.

Ophthalmologists are physicians (MD/MBBS or D.O., not OD or BOptom) who have completed a college degree, medical school, and residency in ophthalmology. Ophthalmology training equips eye specialists to provide the full spectrum of eye care, including the prescription of glasses and contact lenses, medical treatment, and complex microsurgery. In many countries, ophthalmologists also undergo additional specialized training in one of the many subspecialties. Ophthalmology was the first branch of medicine to offer board certification, now a standard practice among all specialties.

In Australia and New Zealand, the FRACO/FRANZCO is the equivalent postgraduate specialist qualification. It is a very competitive speciality to enter training and has a closely monitored and structured training system in place over the five years of postgraduate training. Overseas-trained ophthalmologists are assessed using the pathway published on the RANZCO website. Those who have completed their formal training in the UK and have the CCST/CCT are usually deemed to be comparable.

In Bangladesh to be an ophthalmologist the basic degree is an MBBS. Then they have to obtain a postgraduate degree or diploma in specialty ophthalmology. In Bangladesh, these are Diploma in Ophthalmology, Diploma in Community Ophthalmology, Fellow or Member of the College of Physicians and Surgeons in ophthalmology, and Master of Science in ophthalmology.

In Canada, an ophthalmology residency after medical school is undertaken. The residency lasts a minimum of five years after the MD degree which culminates in fellowship of the Royal College of Surgeons of Canada (FRCSC). Subspecialty training is undertaken by about 30% of fellows (FRCSC) in a variety of fields from anterior segment, cornea, glaucoma, visual rehabilitation, uveitis, oculoplastics, medical and surgical retina, ocular oncology, ocular pathology, or neuro-ophthalmology. About 35 vacancies open per year for ophthalmology residency training in all of Canada. These numbers fluctuate per year, ranging from 30 to 37 spots. Of these, up to seven spots are often dedicated to French-speaking universities in Quebec, while the rest of the English-speaking spots are competed for by hundreds of applicants each year. At the end of the five years, the graduating ophthalmologist must pass the oral and written portions of the Royal College exam.

In Finland, physicians willing to become ophthalmologists must undergo a five-year specialization which includes practical training and theoretical studies.

In India, after completing MBBS degree, postgraduate study in ophthalmology is required. The degrees are Doctor of Medicine, Master of Surgery, Diploma in Ophthalmic Medicine and Surgery, and Diplomate of National Board. The concurrent training and work experience is in the form of a junior residency at a medical college, eye hospital, or institution under the supervision of experienced faculty. Further work experience in form of fellowship, registrar, or senior resident refines the skills of these eye surgeons. All India Ophthalmological Society and various state-level ophthalmological societies hold regular conferences and actively promote continuing medical education.

In Nepal, to become an ophthalmologist, three years postgraduate study is required after completing MBBS degree. The postgraduate degree in ophthalmology is called MD in Ophthalmology. This degree is currently provided by Tilganga Institute of Ophthalmology, Tilganga, Kathmandu, BPKLCO, Institute of Medicine, TU, Kathmandu, BP Koirala Institute of Health Sciences, Dharan, Kathmandu University, Dhulikhel and National Academy of Medical Science, Kathmandu. Few Nepalese citizen also study this subject in Bangladesh, China, India, Pakistan and other countries. All the graduates have to pass Nepal Medical Council Licensing Exam to become a registered Ophthalmology in Nepal. The concurrent residency training is in the form of a PG student (resident) at a medical college, eye hospital, or institution according to the degree providing university's rules and regulations. Nepal Ophthalmic Society holds regular conferences and actively promote continuing medical education.

In Ireland, the Royal College of Surgeons of Ireland grants Membership (MRCSI (Ophth)) and Fellowship (FRCSI (Ophth)) qualifications in conjunction with the Irish College of Ophthalmologists. Total postgraduate training involves an intern year, a minimum of three years of basic surgical training and a further 4.5 years of higher surgical training. Clinical training takes place within public, Health Service Executive-funded hospitals in Dublin, Sligo, Limerick, Galway, Waterford, and Cork. A minimum of 8.5 years of training is required before eligibility to work in consultant posts. Some trainees take extra time to obtain MSc, MD or PhD degrees and to undertake clinical fellowships in the UK, Australia and the United States.

In Pakistan, after MBBS, a four-year full-time residency program leads to an exit-level FCPS examination in ophthalmology, held under the auspices of the College of Physicians and Surgeons, Pakistan. The tough examination is assessed by both highly qualified Pakistani and eminent international ophthalmic consultants. As a prerequisite to the final examinations, an intermediate module, an optics and refraction module, and a dissertation written on a research project carried out under supervision is also assessed. Moreover, a two-and-a-half-year residency program leads to an MCPS while a two-year training of DOMS is also being offered.[21] For candidates in the military, a stringent two-year graded course, with quarterly assessments, is held under Armed Forces Post Graduate Medical Institute in Rawalpindi. The M.S. in ophthalmology is also one of the specialty programs. In addition to programs for doctors, various diplomas and degrees for allied eyecare personnel are also being offered to produce competent optometrists, orthoptists, ophthalmic nurses, ophthalmic technologists, and ophthalmic technicians in this field. These programs are being offered notably by the College of Ophthalmology and Allied Vision Sciences in Lahore and the Pakistan Institute of Community Ophthalmology in Peshawar.[22] Subspecialty fellowships are also being offered in the fields of pediatric ophthalmology and vitreoretinal ophthalmology. King Edward Medical University, Al Shifa Trust Eye Hospital Rawalpindi, and Al- Ibrahim Eye Hospital Karachi have also started a degree program in this field.

Ophthalmology is a considered a medical specialty that uses medicine and surgery to treat diseases of the eye. There are two professional organizations in the country: the Philippine Academy of Ophthalmology (PAO)[23] and the Philippine Academy of Medical Specialists, Discipline in Ophthalmology (PAMS Ophtha). Individually, they regulate ophthalmology residency programs and board certification through their respective accrediting agencies. To become a general ophthalmologist in the Philippines, a candidate must have completed a Doctor of Medicine degree (MD) or its equivalent (e.g. MBBS), have completed an internship in Medicine, have passed the physician licensure exam, and completed residency training at a hospital accredited by the Philippine Board of Ophthalmology (accrediting arm of PAO) [24] or by the Philippine Academy of Medical Specialists, Discipline in Ophthalmology (PAMS Ophtha). Attainment of board certification in ophthalmology from either PBO or PAMS Ophtha is optional, but preferred, in acquiring privileges in most major health institutions. Graduates of residency programs can receive further training in ophthalmology subspecialties, such as neuro-ophthalmology, retina, etc. by completing a fellowship program which varies in length depending on each program's requirements.

In the United Kingdom, three colleges grant postgraduate degrees in ophthalmology. The Royal College of Ophthalmologists (RCOphth) and the Royal College of Surgeons of Edinburgh grant MRCOphth/FRCOphth and MRCSEd/FRCSEd, (although membership is no longer a prerequisite for fellowship), the Royal College of Glasgow grants FRCS. Postgraduate work as a specialist registrar and one of these degrees is required for specialization in eye diseases. Such clinical work is within the NHS, with supplementary private work for some consultants. Only 2.3 ophthalmologists exist per 100,000 population in the UK fewer pro rata than in any other nation in the European Union.[25]

In the United States, four years of residency training after medical school are required, with the first year being an internship in surgery, internal medicine, pediatrics, or a general transition year. Optional fellowships in advanced topics may be pursued for several years after residency. Most currently practicing ophthalmologists train in medical residency programs accredited by the Accreditation Council for Graduate Medical Education or the American Osteopathic Association and are board-certified by the American Board of Ophthalmology or the American Osteopathic Board of Ophthalmology and Otolaryngology. United States physicians who train in osteopathic medical schools hold the Doctor of Osteopathic Medicine (DO) degree rather than an MD degree. The same residency and certification requirements for ophthalmology training must be fulfilled by osteopathic physicians.

Physicians must complete the requirements of continuing medical education to maintain licensure and for recertification. Professional bodies like the American Academy of Ophthalmology and American Society of Cataract and Refractive Surgery organize conferences, help physician members through continuing medical education programs for maintaining board certification, and provide political advocacy and peer support.

Ophthalmology includes subspecialities which deal either with certain diseases or diseases of certain parts of the eye. Some of them are:

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Ophthalmology - Wikipedia

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Regenerative medicine is a branch of translational research[1] in tissue engineering and molecular biology which deals with the "process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function".[2] This field holds the promise of engineering damaged tissues and organs by stimulating the body's own repair mechanisms to functionally heal previously irreparable tissues or organs.[3]

Regenerative medicine also includes the possibility of growing tissues and organs in the laboratory and implanting them when the body cannot heal itself. If a regenerated organ's cells would be derived from the patient's own tissue or cells, this would potentially solve the problem of the shortage of organs available for donation, and the problem of organ transplant rejection.[4][5][6]

Some of the biomedical approaches within the field of regenerative medicine may involve the use of stem cells.[7] Examples include the injection of stem cells or progenitor cells obtained through directed differentiation (cell therapies); the induction of regeneration by biologically active molecules administered alone or as a secretion by infused cells (immunomodulation therapy); and transplantation of in vitro grown organs and tissues (tissue engineering).[8][9]

The term "regenerative medicine" was first used in a 1992 article on hospital administration by Leland Kaiser. Kaisers paper closes with a series of short paragraphs on future technologies that will impact hospitals. One paragraph had "Regenerative Medicine" as a bold print title and stated, "A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems."[10][11]

The widespread use of the term regenerative medicine is attributed to William A. Haseltine (founder of Human Genome Sciences).[12] Haseltine was briefed on the project to isolate human embryonic stem cells and embryonic germ cells at Geron Corporation in collaboration with researchers at the University of Wisconsin-Madison and Johns Hopkins School of Medicine. He recognized that these cells' unique ability to differentiate into all the cell types of the human body (pluripotency) had the potential to develop into a new kind of regenerative therapy.[13][14] Explaining the new class of therapies that such cells could enable, he used the term "regenerative medicine" in the way that it is used today: "an approach to therapy that ... employs human genes, proteins and cells to re-grow, restore or provide mechanical replacements for tissues that have been injured by trauma, damaged by disease or worn by time" and "offers the prospect of curing diseases that cannot be treated effectively today, including those related to aging." [15] From 1995 to 1998 Michael D. West, PhD, organized and managed the research between Geron Corporation and its academic collaborators James Thomson at the University of Wisconsin-Madison and John Gearhart of Johns Hopkins University that led to the first isolation of human embryonic stem and human embryonic germ cells, respectively.[16]

Dr. Stephen Badylak, a Research Professor in the Department of Surgery and director of Tissue Engineering at the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, developed a process for scraping cells from the lining of a pig's bladder, decellularizing (removing cells to leave a clean extracellular structure) the tissue and then drying it to become a sheet or a powder. This extracellular matrix powder was used to regrow the finger of Lee Spievak, who had severed half an inch of his finger after getting it caught in a propeller of a model plane.[17][18][19][dubious discuss] As of 2011, this new technology is being employed by the military on U.S. war veterans in Texas, as well as for some civilian patients. Nicknamed "pixie-dust," the powdered extracellular matrix is being used to successfully regenerate tissue lost and damaged due to traumatic injuries.[20]

In June 2008, at the Hospital Clnic de Barcelona, Professor Paolo Macchiarini and his team, of the University of Barcelona, performed the first tissue engineered trachea (wind pipe) transplantation. Adult stem cells were extracted from the patient's bone marrow, grown into a large population, and matured into cartilage cells, or chondrocytes, using an adaptive method originally devised for treating osteoarthritis. The team then seeded the newly grown chondrocytes, as well as epithileal cells, into a decellularised (free of donor cells) tracheal segment that was donated from a 51-year-old transplant donor who had died of cerebral hemorrhage. After four days of seeding, the graft was used to replace the patient's left main bronchus. After one month, a biopsy elicited local bleeding, indicating that the blood vessels had already grown back successfully.[21][22]

In 2009, the SENS Foundation was launched, with its stated aim as "the application of regenerative medicine defined to include the repair of living cells and extracellular material in situ to the diseases and disabilities of ageing." [23]

In 2012, Professor Paolo Macchiarini and his team improved upon the 2008 implant by transplanting a laboratory-made trachea seeded with the patient's own cells.[24]

On September 12, 2014, surgeons at the Institute of Biomedical Research and Innovation Hospital in Kobe, Japan, transplanted a 1.3 by 3.0 millimeter sheet of retinal pigment epithelium cells, which were differentiated from iPS cells through Directed differentiation, into an eye of an elderly woman, who suffers from age-related macular degeneration.[25]

Because a person's own (autologous) cord blood stem cells can be safely infused back into that individual without being rejected by the body's immune system and because they have unique characteristics compared to other sources of stem cells they are an increasing focus of regenerative medicine research.

The use of cord blood stem cells in treating conditions such as brain injury[26] and Type 1 Diabetes[27] is already being studied in humans, and earlier stage research is being conducted for treatments of stroke,[28][29] and hearing loss.[30]

Current estimates indicate that approximately 1 in 3 Americans could benefit from regenerative medicine.[31] With autologous (the person's own) cells, there is no risk of the immune system rejecting the cells.

Researchers are exploring the use of cord blood stem cells for a spectrum of regenerative medicine applications, including the following:

A clinical trial under way at the University of Florida is examining how an infusion of autologous cord blood stem cells into children with Type 1 diabetes will impact metabolic control over time, as compared to standard insulin treatments. Preliminary results demonstrate that an infusion of cord blood stem cell is safe and may provide some slowing of the loss of insulin production in children with type 1 diabetes.[32]

The stem cells found in a newborn's umbilical cord blood are holding great promise in cardiovascular repair. Researchers are noting several positive observations in pre-clinical animal studies. Thus far, in animal models of myocardial infarction, cord blood stem cells have shown the ability to selectively migrate to injured cardiac tissue, improve vascular function and blood flow at the site of injury, and improve overall heart function.[31]

Research has demonstrated convincing evidence in animal models that cord blood stem cells injected intravenously have the ability to migrate to the area of brain injury, alleviating mobility related symptoms.[33][34] Also, administration of human cord blood stem cells into animals with stroke was shown to significantly improve behavior by stimulating the creation of new blood vessels and neurons in the brain.[35]

This research also lends support for the pioneering clinical work at Duke University, focused on evaluating the impact of autologous cord blood infusions in children diagnosed with cerebral palsy and other forms of brain injury. This study is examining if an infusion of the child's own cord blood stem cells facilitates repair of damaged brain tissue, including many with cerebral palsy. To date, more than 100 children have participated in the experimental treatment many whose parents are reporting good progress.[36]

Another report published encouraging results in 2 toddlers with cerebral palsy where autologous cord blood infusion was combined with G-CSF.[37]

As these clinical and pre-clinical studies demonstrate, cord blood stem cells will likely be an important resource as medicine advances toward harnessing the body's own cells for treatment. The field of regenerative medicine can be expected to benefit greatly as additional cord blood stem cell applications are researched and more people have access to their own preserved cord blood. [38]

On May 17, 2012, Osiris Therapeutics announced that Canadian health regulators approved Prochymal, a drug for acute graft-versus-host disease in children who have failed to respond to steroid treatment. Prochymal is the first stem cell drug to be approved anywhere in the world for a systemic disease. Graft-versus-host disease, a potentially fatal complication from bone marrow transplant, involves the newly implanted cells attacking the patient's body.[39]

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Regenerative medicine - Wikipedia

Deoxyribonucleic acid (i;[1]DNA) is a molecule that carries the genetic instructions used in the growth, development, functioning and reproduction of all known living organisms and many viruses. DNA and RNA are nucleic acids; alongside proteins, lipids and complex carbohydrates (polysaccharides), they are one of the four major types of macromolecules that are essential for all known forms of life. Most DNA molecules consist of two biopolymer strands coiled around each other to form a double helix.

The two DNA strands are termed polynucleotides since they are composed of simpler monomer units called nucleotides.[2][3] Each nucleotide is composed of one of four nitrogen-containing nucleobaseseither cytosine (C), guanine (G), adenine (A), or thymine (T)and a sugar called deoxyribose and a phosphate group. The nucleotides are joined to one another in a chain by covalent bonds between the sugar of one nucleotide and the phosphate of the next, resulting in an alternating sugar-phosphate backbone. The nitrogenous bases of the two separate polynucleotide strands are bound together (according to base pairing rules (A with T, and C with G) with hydrogen bonds to make double-stranded DNA. The total amount of related DNA base pairs on Earth is estimated at 5.0 x 1037, and weighs 50 billion tonnes.[4] In comparison, the total mass of the biosphere has been estimated to be as much as 4 trillion tons of carbon (TtC).[5]

DNA stores biological information. The DNA backbone is resistant to cleavage, and both strands of the double-stranded structure store the same biological information. This information is replicated as and when the two strands separate. A large part of DNA (more than 98% for humans) is non-coding, meaning that these sections do not serve as patterns for protein sequences.

The two strands of DNA run in opposite directions to each other and are thus antiparallel. Attached to each sugar is one of four types of nucleobases (informally, bases). It is the sequence of these four nucleobases along the backbone that encodes biological information. RNA strands are created using DNA strands as a template in a process called transcription. Under the genetic code, these RNA strands are translated to specify the sequence of amino acids within proteins in a process called translation.

Within eukaryotic cells, DNA is organized into long structures called chromosomes. During cell division these chromosomes are duplicated in the process of DNA replication, providing each cell its own complete set of chromosomes. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA in organelles, such as mitochondria or chloroplasts.[6] In contrast, prokaryotes (bacteria and archaea) store their DNA only in the cytoplasm. Within the eukaryotic chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

DNA was first isolated by Friedrich Miescher in 1869. Its molecular structure was identified by James Watson and Francis Crick in 1953, whose model-building efforts were guided by X-ray diffraction data acquired by Rosalind Franklin. DNA is used by researchers as a molecular tool to explore physical laws and theories, such as the ergodic theorem and the theory of elasticity. The unique material properties of DNA have made it an attractive molecule for material scientists and engineers interested in micro- and nano-fabrication. Among notable advances in this field are DNA origami and DNA-based hybrid materials.[7]

DNA is a long polymer made from repeating units called nucleotides.[8][9] The structure of DNA is non-static,[10] all species comprises two helical chains each coiled round the same axis, and each with a pitch of 34ngstrms (3.4nanometres) and a radius of 10ngstrms (1.0nanometre).[11] According to another study, when measured in a particular solution, the DNA chain measured 22 to 26ngstrms wide (2.2 to 2.6nanometres), and one nucleotide unit measured 3.3 (0.33nm) long.[12] Although each individual repeating unit is very small, DNA polymers can be very large molecules containing millions of nucleotides. For instance, the DNA in the largest human chromosome, chromosome number 1, consists of approximately 220 million base pairs[13] and would be 85mm long if straightened.

In living organisms DNA does not usually exist as a single molecule, but instead as a pair of molecules that are held tightly together.[14][15] These two long strands entwine like vines, in the shape of a double helix. The nucleotide contains both a segment of the backbone of the molecule (which holds the chain together) and a nucleobase (which interacts with the other DNA strand in the helix). A nucleobase linked to a sugar is called a nucleoside and a base linked to a sugar and one or more phosphate groups is called a nucleotide. A polymer comprising multiple linked nucleotides (as in DNA) is called a polynucleotide.[16]

The backbone of the DNA strand is made from alternating phosphate and sugar residues.[17] The sugar in DNA is 2-deoxyribose, which is a pentose (five-carbon) sugar. The sugars are joined together by phosphate groups that form phosphodiester bonds between the third and fifth carbon atoms of adjacent sugar rings. These asymmetric bonds mean a strand of DNA has a direction. In a double helix, the direction of the nucleotides in one strand is opposite to their direction in the other strand: the strands are antiparallel. The asymmetric ends of DNA strands are said to have a directionality of five prime (5) and three prime (3), with the 5 end having a terminal phosphate group and the 3 end a terminal hydroxyl group. One major difference between DNA and RNA is the sugar, with the 2-deoxyribose in DNA being replaced by the alternative pentose sugar ribose in RNA.[15]

The DNA double helix is stabilized primarily by two forces: hydrogen bonds between nucleotides and base-stacking interactions among aromatic nucleobases.[19] In the aqueous environment of the cell, the conjugated bonds of nucleotide bases align perpendicular to the axis of the DNA molecule, minimizing their interaction with the solvation shell. The four bases found in DNA are adenine (A), cytosine (C), guanine (G) and thymine (T). These four bases are attached to the sugar-phosphate to form the complete nucleotide, as shown for adenosine monophosphate. Adenine pairs with thymine and guanine pairs with cytosine. It was represented by A-T base pairs and G-C base pairs.[20][21]

The nucleobases are classified into two types: the purines, A and G, being fused five- and six-membered heterocyclic compounds, and the pyrimidines, the six-membered rings C and T.[15] A fifth pyrimidine nucleobase, uracil (U), usually takes the place of thymine in RNA and differs from thymine by lacking a methyl group on its ring. In addition to RNA and DNA, many artificial nucleic acid analogues have been created to study the properties of nucleic acids, or for use in biotechnology.[22]

Uracil is not usually found in DNA, occurring only as a breakdown product of cytosine. However, in several bacteriophages, Bacillus subtilis bacteriophages PBS1 and PBS2 and Yersinia bacteriophage piR1-37, thymine has been replaced by uracil.[23] Another phage - Staphylococcal phage S6 - has been identified with a genome where thymine has been replaced by uracil.[24]

Base J (beta-d-glucopyranosyloxymethyluracil), a modified form of uracil, is also found in several organisms: the flagellates Diplonema and Euglena, and all the kinetoplastid genera.[25] Biosynthesis of J occurs in two steps: in the first step a specific thymidine in DNA is converted into hydroxymethyldeoxyuridine; in the second HOMedU is glycosylated to form J.[26] Proteins that bind specifically to this base have been identified.[27][28][29] These proteins appear to be distant relatives of the Tet1 oncogene that is involved in the pathogenesis of acute myeloid leukemia.[30] J appears to act as a termination signal for RNA polymerase II.[31][32]

Twin helical strands form the DNA backbone. Another double helix may be found tracing the spaces, or grooves, between the strands. These voids are adjacent to the base pairs and may provide a binding site. As the strands are not symmetrically located with respect to each other, the grooves are unequally sized. One groove, the major groove, is 22 wide and the other, the minor groove, is 12 wide.[33] The width of the major groove means that the edges of the bases are more accessible in the major groove than in the minor groove. As a result, proteins such as transcription factors that can bind to specific sequences in double-stranded DNA usually make contact with the sides of the bases exposed in the major groove.[34] This situation varies in unusual conformations of DNA within the cell (see below), but the major and minor grooves are always named to reflect the differences in size that would be seen if the DNA is twisted back into the ordinary B form.

In a DNA double helix, each type of nucleobase on one strand bonds with just one type of nucleobase on the other strand. This is called complementary base pairing. Here, purines form hydrogen bonds to pyrimidines, with adenine bonding only to thymine in two hydrogen bonds, and cytosine bonding only to guanine in three hydrogen bonds. This arrangement of two nucleotides binding together across the double helix is called a base pair. As hydrogen bonds are not covalent, they can be broken and rejoined relatively easily. The two strands of DNA in a double helix can thus be pulled apart like a zipper, either by a mechanical force or high temperature.[35] As a result of this base pair complementarity, all the information in the double-stranded sequence of a DNA helix is duplicated on each strand, which is vital in DNA replication. This reversible and specific interaction between complementary base pairs is critical for all the functions of DNA in living organisms.[9]

The two types of base pairs form different numbers of hydrogen bonds, AT forming two hydrogen bonds, and GC forming three hydrogen bonds (see figures, right). DNA with high GC-content is more stable than DNA with low GC-content.

As noted above, most DNA molecules are actually two polymer strands, bound together in a helical fashion by noncovalent bonds; this double stranded structure (dsDNA) is maintained largely by the intrastrand base stacking interactions, which are strongest for G,C stacks. The two strands can come apart a process known as melting to form two single-stranded DNA molecules (ssDNA) molecules. Melting occurs at high temperature, low salt and high pH (low pH also melts DNA, but since DNA is unstable due to acid depurination, low pH is rarely used).

The stability of the dsDNA form depends not only on the GC-content (% G,C basepairs) but also on sequence (since stacking is sequence specific) and also length (longer molecules are more stable). The stability can be measured in various ways; a common way is the "melting temperature", which is the temperature at which 50% of the ds molecules are converted to ss molecules; melting temperature is dependent on ionic strength and the concentration of DNA. As a result, it is both the percentage of GC base pairs and the overall length of a DNA double helix that determines the strength of the association between the two strands of DNA. Long DNA helices with a high GC-content have stronger-interacting strands, while short helices with high AT content have weaker-interacting strands.[36] In biology, parts of the DNA double helix that need to separate easily, such as the TATAAT Pribnow box in some promoters, tend to have a high AT content, making the strands easier to pull apart.[37]

In the laboratory, the strength of this interaction can be measured by finding the temperature necessary to break the hydrogen bonds, their melting temperature (also called Tm value). When all the base pairs in a DNA double helix melt, the strands separate and exist in solution as two entirely independent molecules. These single-stranded DNA molecules (ssDNA) have no single common shape, but some conformations are more stable than others.[38]

A DNA sequence is called "sense" if its sequence is the same as that of a messenger RNA copy that is translated into protein.[39] The sequence on the opposite strand is called the "antisense" sequence. Both sense and antisense sequences can exist on different parts of the same strand of DNA (i.e. both strands can contain both sense and antisense sequences). In both prokaryotes and eukaryotes, antisense RNA sequences are produced, but the functions of these RNAs are not entirely clear.[40] One proposal is that antisense RNAs are involved in regulating gene expression through RNA-RNA base pairing.[41]

A few DNA sequences in prokaryotes and eukaryotes, and more in plasmids and viruses, blur the distinction between sense and antisense strands by having overlapping genes.[42] In these cases, some DNA sequences do double duty, encoding one protein when read along one strand, and a second protein when read in the opposite direction along the other strand. In bacteria, this overlap may be involved in the regulation of gene transcription,[43] while in viruses, overlapping genes increase the amount of information that can be encoded within the small viral genome.[44]

DNA can be twisted like a rope in a process called DNA supercoiling. With DNA in its "relaxed" state, a strand usually circles the axis of the double helix once every 10.4 base pairs, but if the DNA is twisted the strands become more tightly or more loosely wound.[45] If the DNA is twisted in the direction of the helix, this is positive supercoiling, and the bases are held more tightly together. If they are twisted in the opposite direction, this is negative supercoiling, and the bases come apart more easily. In nature, most DNA has slight negative supercoiling that is introduced by enzymes called topoisomerases.[46] These enzymes are also needed to relieve the twisting stresses introduced into DNA strands during processes such as transcription and DNA replication.[47]

DNA exists in many possible conformations that include A-DNA, B-DNA, and Z-DNA forms, although, only B-DNA and Z-DNA have been directly observed in functional organisms.[17] The conformation that DNA adopts depends on the hydration level, DNA sequence, the amount and direction of supercoiling, chemical modifications of the bases, the type and concentration of metal ions, and the presence of polyamines in solution.[48]

The first published reports of A-DNA X-ray diffraction patternsand also B-DNAused analyses based on Patterson transforms that provided only a limited amount of structural information for oriented fibers of DNA.[49][50] An alternative analysis was then proposed by Wilkins et al., in 1953, for the in vivo B-DNA X-ray diffraction-scattering patterns of highly hydrated DNA fibers in terms of squares of Bessel functions.[51] In the same journal, James Watson and Francis Crick presented their molecular modeling analysis of the DNA X-ray diffraction patterns to suggest that the structure was a double-helix.[11]

Although the B-DNA form is most common under the conditions found in cells,[52] it is not a well-defined conformation but a family of related DNA conformations[53] that occur at the high hydration levels present in living cells. Their corresponding X-ray diffraction and scattering patterns are characteristic of molecular paracrystals with a significant degree of disorder.[54][55]

Compared to B-DNA, the A-DNA form is a wider right-handed spiral, with a shallow, wide minor groove and a narrower, deeper major groove. The A form occurs under non-physiological conditions in partly dehydrated samples of DNA, while in the cell it may be produced in hybrid pairings of DNA and RNA strands, and in enzyme-DNA complexes.[56][57] Segments of DNA where the bases have been chemically modified by methylation may undergo a larger change in conformation and adopt the Z form. Here, the strands turn about the helical axis in a left-handed spiral, the opposite of the more common B form.[58] These unusual structures can be recognized by specific Z-DNA binding proteins and may be involved in the regulation of transcription.[59]

For many years exobiologists have proposed the existence of a shadow biosphere, a postulated microbial biosphere of Earth that uses radically different biochemical and molecular processes than currently known life. One of the proposals was the existence of lifeforms that use arsenic instead of phosphorus in DNA. A report in 2010 of the possibility in the bacterium GFAJ-1, was announced,[60][60][61] though the research was disputed,[61][62] and evidence suggests the bacterium actively prevents the incorporation of arsenic into the DNA backbone and other biomolecules.[63]

At the ends of the linear chromosomes are specialized regions of DNA called telomeres. The main function of these regions is to allow the cell to replicate chromosome ends using the enzyme telomerase, as the enzymes that normally replicate DNA cannot copy the extreme 3 ends of chromosomes.[64] These specialized chromosome caps also help protect the DNA ends, and stop the DNA repair systems in the cell from treating them as damage to be corrected.[65] In human cells, telomeres are usually lengths of single-stranded DNA containing several thousand repeats of a simple TTAGGG sequence.[66]

These guanine-rich sequences may stabilize chromosome ends by forming structures of stacked sets of four-base units, rather than the usual base pairs found in other DNA molecules. Here, four guanine bases form a flat plate and these flat four-base units then stack on top of each other, to form a stable G-quadruplex structure.[68] These structures are stabilized by hydrogen bonding between the edges of the bases and chelation of a metal ion in the centre of each four-base unit.[69] Other structures can also be formed, with the central set of four bases coming from either a single strand folded around the bases, or several different parallel strands, each contributing one base to the central structure.

In addition to these stacked structures, telomeres also form large loop structures called telomere loops, or T-loops. Here, the single-stranded DNA curls around in a long circle stabilized by telomere-binding proteins.[70] At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere strand disrupting the double-helical DNA and base pairing to one of the two strands. This triple-stranded structure is called a displacement loop or D-loop.[68]

In DNA, fraying occurs when non-complementary regions exist at the end of an otherwise complementary double-strand of DNA. However, branched DNA can occur if a third strand of DNA is introduced and contains adjoining regions able to hybridize with the frayed regions of the pre-existing double-strand. Although the simplest example of branched DNA involves only three strands of DNA, complexes involving additional strands and multiple branches are also possible.[71] Branched DNA can be used in nanotechnology to construct geometric shapes, see the section on uses in technology below.

The expression of genes is influenced by how the DNA is packaged in chromosomes, in a structure called chromatin. Base modifications can be involved in packaging, with regions that have low or no gene expression usually containing high levels of methylation of cytosine bases. DNA packaging and its influence on gene expression can also occur by covalent modifications of the histone protein core around which DNA is wrapped in the chromatin structure or else by remodeling carried out by chromatin remodeling complexes (see Chromatin remodeling). There is, further, crosstalk between DNA methylation and histone modification, so they can coordinately affect chromatin and gene expression.[72]

For one example, cytosine methylation, produces 5-methylcytosine, which is important for X-inactivation of chromosomes.[73] The average level of methylation varies between organisms the worm Caenorhabditis elegans lacks cytosine methylation, while vertebrates have higher levels, with up to 1% of their DNA containing 5-methylcytosine.[74] Despite the importance of 5-methylcytosine, it can deaminate to leave a thymine base, so methylated cytosines are particularly prone to mutations.[75] Other base modifications include adenine methylation in bacteria, the presence of 5-hydroxymethylcytosine in the brain,[76] and the glycosylation of uracil to produce the "J-base" in kinetoplastids.[77][78]

DNA can be damaged by many sorts of mutagens, which change the DNA sequence. Mutagens include oxidizing agents, alkylating agents and also high-energy electromagnetic radiation such as ultraviolet light and X-rays. The type of DNA damage produced depends on the type of mutagen. For example, UV light can damage DNA by producing thymine dimers, which are cross-links between pyrimidine bases.[80] On the other hand, oxidants such as free radicals or hydrogen peroxide produce multiple forms of damage, including base modifications, particularly of guanosine, and double-strand breaks.[81] A typical human cell contains about 150,000 bases that have suffered oxidative damage.[82] Of these oxidative lesions, the most dangerous are double-strand breaks, as these are difficult to repair and can produce point mutations, insertions, deletions from the DNA sequence, and chromosomal translocations.[83] These mutations can cause cancer. Because of inherent limits in the DNA repair mechanisms, if humans lived long enough, they would all eventually develop cancer.[84][85] DNA damages that are naturally occurring, due to normal cellular processes that produce reactive oxygen species, the hydrolytic activities of cellular water, etc., also occur frequently. Although most of these damages are repaired, in any cell some DNA damage may remain despite the action of repair processes. These remaining DNA damages accumulate with age in mammalian postmitotic tissues. This accumulation appears to be an important underlying cause of aging.[86][87][88]

Many mutagens fit into the space between two adjacent base pairs, this is called intercalation. Most intercalators are aromatic and planar molecules; examples include ethidium bromide, acridines, daunomycin, and doxorubicin. For an intercalator to fit between base pairs, the bases must separate, distorting the DNA strands by unwinding of the double helix. This inhibits both transcription and DNA replication, causing toxicity and mutations.[89] As a result, DNA intercalators may be carcinogens, and in the case of thalidomide, a teratogen.[90] Others such as benzo[a]pyrene diol epoxide and aflatoxin form DNA adducts that induce errors in replication.[91] Nevertheless, due to their ability to inhibit DNA transcription and replication, other similar toxins are also used in chemotherapy to inhibit rapidly growing cancer cells.[92]

DNA usually occurs as linear chromosomes in eukaryotes, and circular chromosomes in prokaryotes. The set of chromosomes in a cell makes up its genome; the human genome has approximately 3 billion base pairs of DNA arranged into 46 chromosomes.[93] The information carried by DNA is held in the sequence of pieces of DNA called genes. Transmission of genetic information in genes is achieved via complementary base pairing. For example, in transcription, when a cell uses the information in a gene, the DNA sequence is copied into a complementary RNA sequence through the attraction between the DNA and the correct RNA nucleotides. Usually, this RNA copy is then used to make a matching protein sequence in a process called translation, which depends on the same interaction between RNA nucleotides. In alternative fashion, a cell may simply copy its genetic information in a process called DNA replication. The details of these functions are covered in other articles; here the focus is on the interactions between DNA and other molecules that mediate the function of the genome.

Genomic DNA is tightly and orderly packed in the process called DNA condensation, to fit the small available volumes of the cell. In eukaryotes, DNA is located in the cell nucleus, with small amounts in mitochondria and chloroplasts. In prokaryotes, the DNA is held within an irregularly shaped body in the cytoplasm called the nucleoid.[94] The genetic information in a genome is held within genes, and the complete set of this information in an organism is called its genotype. A gene is a unit of heredity and is a region of DNA that influences a particular characteristic in an organism. Genes contain an open reading frame that can be transcribed, and regulatory sequences such as promoters and enhancers, which control transcription of the open reading frame.

In many species, only a small fraction of the total sequence of the genome encodes protein. For example, only about 1.5% of the human genome consists of protein-coding exons, with over 50% of human DNA consisting of non-coding repetitive sequences.[95] The reasons for the presence of so much noncoding DNA in eukaryotic genomes and the extraordinary differences in genome size, or C-value, among species represent a long-standing puzzle known as the "C-value enigma".[96] However, some DNA sequences that do not code protein may still encode functional non-coding RNA molecules, which are involved in the regulation of gene expression.[97]

Some noncoding DNA sequences play structural roles in chromosomes. Telomeres and centromeres typically contain few genes, but are important for the function and stability of chromosomes.[65][99] An abundant form of noncoding DNA in humans are pseudogenes, which are copies of genes that have been disabled by mutation.[100] These sequences are usually just molecular fossils, although they can occasionally serve as raw genetic material for the creation of new genes through the process of gene duplication and divergence.[101]

A gene is a sequence of DNA that contains genetic information and can influence the phenotype of an organism. Within a gene, the sequence of bases along a DNA strand defines a messenger RNA sequence, which then defines one or more protein sequences. The relationship between the nucleotide sequences of genes and the amino-acid sequences of proteins is determined by the rules of translation, known collectively as the genetic code. The genetic code consists of three-letter 'words' called codons formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT).

In transcription, the codons of a gene are copied into messenger RNA by RNA polymerase. This RNA copy is then decoded by a ribosome that reads the RNA sequence by base-pairing the messenger RNA to transfer RNA, which carries amino acids. Since there are 4 bases in 3-letter combinations, there are 64 possible codons (43combinations). These encode the twenty standard amino acids, giving most amino acids more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region; these are the TAA, TGA, and TAG codons.

Cell division is essential for an organism to grow, but, when a cell divides, it must replicate the DNA in its genome so that the two daughter cells have the same genetic information as their parent. The double-stranded structure of DNA provides a simple mechanism for DNA replication. Here, the two strands are separated and then each strand's complementary DNA sequence is recreated by an enzyme called DNA polymerase. This enzyme makes the complementary strand by finding the correct base through complementary base pairing, and bonding it onto the original strand. As DNA polymerases can only extend a DNA strand in a 5 to 3 direction, different mechanisms are used to copy the antiparallel strands of the double helix.[102] In this way, the base on the old strand dictates which base appears on the new strand, and the cell ends up with a perfect copy of its DNA.

Naked extracellular DNA (eDNA), most of it released by cell death, is nearly ubiquitous in the environment. Its concentration in soil may be as high as 2 g/L, and its concentration in natural aquatic environments may be as high at 88 g/L.[103] Various possible functions have been proposed for eDNA: it may be involved in horizontal gene transfer;[104] it may provide nutrients;[105] and it may act as a buffer to recruit or titrate ions or antibiotics.[106] Extracellular DNA acts as a functional extracellular matrix component in the biofilms of several bacterial species. It may act as a recognition factor to regulate the attachment and dispersal of specific cell types in the biofilm;[107] it may contribute to biofilm formation;[108] and it may contribute to the biofilm's physical strength and resistance to biological stress.[109]

All the functions of DNA depend on interactions with proteins. These protein interactions can be non-specific, or the protein can bind specifically to a single DNA sequence. Enzymes can also bind to DNA and of these, the polymerases that copy the DNA base sequence in transcription and DNA replication are particularly important.

Structural proteins that bind DNA are well-understood examples of non-specific DNA-protein interactions. Within chromosomes, DNA is held in complexes with structural proteins. These proteins organize the DNA into a compact structure called chromatin. In eukaryotes this structure involves DNA binding to a complex of small basic proteins called histones, while in prokaryotes multiple types of proteins are involved.[110][111] The histones form a disk-shaped complex called a nucleosome, which contains two complete turns of double-stranded DNA wrapped around its surface. These non-specific interactions are formed through basic residues in the histones, making ionic bonds to the acidic sugar-phosphate backbone of the DNA, and are thus largely independent of the base sequence.[112] Chemical modifications of these basic amino acid residues include methylation, phosphorylation and acetylation.[113] These chemical changes alter the strength of the interaction between the DNA and the histones, making the DNA more or less accessible to transcription factors and changing the rate of transcription.[114] Other non-specific DNA-binding proteins in chromatin include the high-mobility group proteins, which bind to bent or distorted DNA.[115] These proteins are important in bending arrays of nucleosomes and arranging them into the larger structures that make up chromosomes.[116]

A distinct group of DNA-binding proteins are the DNA-binding proteins that specifically bind single-stranded DNA. In humans, replication protein A is the best-understood member of this family and is used in processes where the double helix is separated, including DNA replication, recombination and DNA repair.[117] These binding proteins seem to stabilize single-stranded DNA and protect it from forming stem-loops or being degraded by nucleases.

In contrast, other proteins have evolved to bind to particular DNA sequences. The most intensively studied of these are the various transcription factors, which are proteins that regulate transcription. Each transcription factor binds to one particular set of DNA sequences and activates or inhibits the transcription of genes that have these sequences close to their promoters. The transcription factors do this in two ways. Firstly, they can bind the RNA polymerase responsible for transcription, either directly or through other mediator proteins; this locates the polymerase at the promoter and allows it to begin transcription.[119] Alternatively, transcription factors can bind enzymes that modify the histones at the promoter. This changes the accessibility of the DNA template to the polymerase.[120]

As these DNA targets can occur throughout an organism's genome, changes in the activity of one type of transcription factor can affect thousands of genes.[121] Consequently, these proteins are often the targets of the signal transduction processes that control responses to environmental changes or cellular differentiation and development. The specificity of these transcription factors' interactions with DNA come from the proteins making multiple contacts to the edges of the DNA bases, allowing them to "read" the DNA sequence. Most of these base-interactions are made in the major groove, where the bases are most accessible.[34]

Nucleases are enzymes that cut DNA strands by catalyzing the hydrolysis of the phosphodiester bonds. Nucleases that hydrolyse nucleotides from the ends of DNA strands are called exonucleases, while endonucleases cut within strands. The most frequently used nucleases in molecular biology are the restriction endonucleases, which cut DNA at specific sequences. For instance, the EcoRV enzyme shown to the left recognizes the 6-base sequence 5-GATATC-3 and makes a cut at the horizontal line. In nature, these enzymes protect bacteria against phage infection by digesting the phage DNA when it enters the bacterial cell, acting as part of the restriction modification system.[123] In technology, these sequence-specific nucleases are used in molecular cloning and DNA fingerprinting.

Enzymes called DNA ligases can rejoin cut or broken DNA strands.[124] Ligases are particularly important in lagging strand DNA replication, as they join together the short segments of DNA produced at the replication fork into a complete copy of the DNA template. They are also used in DNA repair and genetic recombination.[124]

Topoisomerases are enzymes with both nuclease and ligase activity. These proteins change the amount of supercoiling in DNA. Some of these enzymes work by cutting the DNA helix and allowing one section to rotate, thereby reducing its level of supercoiling; the enzyme then seals the DNA break.[46] Other types of these enzymes are capable of cutting one DNA helix and then passing a second strand of DNA through this break, before rejoining the helix.[125] Topoisomerases are required for many processes involving DNA, such as DNA replication and transcription.[47]

Helicases are proteins that are a type of molecular motor. They use the chemical energy in nucleoside triphosphates, predominantly adenosine triphosphate (ATP), to break hydrogen bonds between bases and unwind the DNA double helix into single strands.[126] These enzymes are essential for most processes where enzymes need to access the DNA bases.

Polymerases are enzymes that synthesize polynucleotide chains from nucleoside triphosphates. The sequence of their products are created based on existing polynucleotide chainswhich are called templates. These enzymes function by repeatedly adding a nucleotide to the 3 hydroxyl group at the end of the growing polynucleotide chain. As a consequence, all polymerases work in a 5 to 3 direction.[127] In the active site of these enzymes, the incoming nucleoside triphosphate base-pairs to the template: this allows polymerases to accurately synthesize the complementary strand of their template. Polymerases are classified according to the type of template that they use.

In DNA replication, DNA-dependent DNA polymerases make copies of DNA polynucleotide chains. To preserve biological information, it is essential that the sequence of bases in each copy are precisely complementary to the sequence of bases in the template strand. Many DNA polymerases have a proofreading activity. Here, the polymerase recognizes the occasional mistakes in the synthesis reaction by the lack of base pairing between the mismatched nucleotides. If a mismatch is detected, a 3 to 5 exonuclease activity is activated and the incorrect base removed.[128] In most organisms, DNA polymerases function in a large complex called the replisome that contains multiple accessory subunits, such as the DNA clamp or helicases.[129]

RNA-dependent DNA polymerases are a specialized class of polymerases that copy the sequence of an RNA strand into DNA. They include reverse transcriptase, which is a viral enzyme involved in the infection of cells by retroviruses, and telomerase, which is required for the replication of telomeres.[64][130] Telomerase is an unusual polymerase because it contains its own RNA template as part of its structure.[65]

Transcription is carried out by a DNA-dependent RNA polymerase that copies the sequence of a DNA strand into RNA. To begin transcribing a gene, the RNA polymerase binds to a sequence of DNA called a promoter and separates the DNA strands. It then copies the gene sequence into a messenger RNA transcript until it reaches a region of DNA called the terminator, where it halts and detaches from the DNA. As with human DNA-dependent DNA polymerases, RNA polymerase II, the enzyme that transcribes most of the genes in the human genome, operates as part of a large protein complex with multiple regulatory and accessory subunits.[131]

A DNA helix usually does not interact with other segments of DNA, and in human cells the different chromosomes even occupy separate areas in the nucleus called "chromosome territories".[133] This physical separation of different chromosomes is important for the ability of DNA to function as a stable repository for information, as one of the few times chromosomes interact is in chromosomal crossover which occurs during sexual reproduction, when genetic recombination occurs. Chromosomal crossover is when two DNA helices break, swap a section and then rejoin.

Recombination allows chromosomes to exchange genetic information and produces new combinations of genes, which increases the efficiency of natural selection and can be important in the rapid evolution of new proteins.[134] Genetic recombination can also be involved in DNA repair, particularly in the cell's response to double-strand breaks.[135]

The most common form of chromosomal crossover is homologous recombination, where the two chromosomes involved share very similar sequences. Non-homologous recombination can be damaging to cells, as it can produce chromosomal translocations and genetic abnormalities. The recombination reaction is catalyzed by enzymes known as recombinases, such as RAD51.[136] The first step in recombination is a double-stranded break caused by either an endonuclease or damage to the DNA.[137] A series of steps catalyzed in part by the recombinase then leads to joining of the two helices by at least one Holliday junction, in which a segment of a single strand in each helix is annealed to the complementary strand in the other helix. The Holliday junction is a tetrahedral junction structure that can be moved along the pair of chromosomes, swapping one strand for another. The recombination reaction is then halted by cleavage of the junction and re-ligation of the released DNA.[138]

DNA contains the genetic information that allows all modern living things to function, grow and reproduce. However, it is unclear how long in the 4-billion-year history of life DNA has performed this function, as it has been proposed that the earliest forms of life may have used RNA as their genetic material.[139][140] RNA may have acted as the central part of early cell metabolism as it can both transmit genetic information and carry out catalysis as part of ribozymes.[141] This ancient RNA world where nucleic acid would have been used for both catalysis and genetics may have influenced the evolution of the current genetic code based on four nucleotide bases. This would occur, since the number of different bases in such an organism is a trade-off between a small number of bases increasing replication accuracy and a large number of bases increasing the catalytic efficiency of ribozymes.[142] However, there is no direct evidence of ancient genetic systems, as recovery of DNA from most fossils is impossible because DNA survives in the environment for less than one million years, and slowly degrades into short fragments in solution.[143] Claims for older DNA have been made, most notably a report of the isolation of a viable bacterium from a salt crystal 250 million years old,[144] but these claims are controversial.[145][146]

Building blocks of DNA (adenine, guanine and related organic molecules) may have been formed extraterrestrially in outer space.[147][148][149] Complex DNA and RNA organic compounds of life, including uracil, cytosine, and thymine, have also been formed in the laboratory under conditions mimicking those found in outer space, using starting chemicals, such as pyrimidine, found in meteorites. Pyrimidine, like polycyclic aromatic hydrocarbons (PAHs), the most carbon-rich chemical found in the universe, may have been formed in red giants or in interstellar cosmic dust and gas clouds.[150]

Methods have been developed to purify DNA from organisms, such as phenol-chloroform extraction, and to manipulate it in the laboratory, such as restriction digests and the polymerase chain reaction. Modern biology and biochemistry make intensive use of these techniques in recombinant DNA technology. Recombinant DNA is a man-made DNA sequence that has been assembled from other DNA sequences. They can be transformed into organisms in the form of plasmids or in the appropriate format, by using a viral vector.[151] The genetically modified organisms produced can be used to produce products such as recombinant proteins, used in medical research,[152] or be grown in agriculture.[153][154]

Forensic scientists can use DNA in blood, semen, skin, saliva or hair found at a crime scene to identify a matching DNA of an individual, such as a perpetrator. This process is formally termed DNA profiling, but may also be called "genetic fingerprinting". In DNA profiling, the lengths of variable sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared between people. This method is usually an extremely reliable technique for identifying a matching DNA.[155] However, identification can be complicated if the scene is contaminated with DNA from several people.[156] DNA profiling was developed in 1984 by British geneticist Sir Alec Jeffreys,[157] and first used in forensic science to convict Colin Pitchfork in the 1988 Enderby murders case.[158]

The development of forensic science, and the ability to now obtain genetic matching on minute samples of blood, skin, saliva, or hair has led to re-examining many cases. Evidence can now be uncovered that was scientifically impossible at the time of the original examination. Combined with the removal of the double jeopardy law in some places, this can allow cases to be reopened where prior trials have failed to produce sufficient evidence to convince a jury. People charged with serious crimes may be required to provide a sample of DNA for matching purposes. The most obvious defence to DNA matches obtained forensically is to claim that cross-contamination of evidence has occurred. This has resulted in meticulous strict handling procedures with new cases of serious crime. DNA profiling is also used successfully to positively identify victims of mass casualty incidents,[159] bodies or body parts in serious accidents, and individual victims in mass war graves, via matching to family members.

DNA profiling is also used in DNA paternity testing to determine if someone is the biological parent or grandparent of a child with the probability of parentage is typically 99.99% when the alleged parent is biologically related to the child. Normal DNA sequencing methods happen after birth but there are new methods to test paternity while a mother is still pregnant.[160]

Deoxyribozymes, also called DNAzymes or catalytic DNA are first discovered in 1994.[161] They are mostly single stranded DNA sequences isolated from a large pool of random DNA sequences through a combinatorial approach called in vitro selection or systematic evolution of ligands by exponential enrichment (SELEX). DNAzymes catalyze variety of chemical reactions including RNA-DNA cleavage, RNA-DNA ligation, amino acids phosphorylation-dephosphorylation, carbon-carbon bond formation, and etc. DNAzymes can enhance catalytic rate of chemical reactions up to 100,000,000,000-fold over the uncatalyzed reaction.[162] The most extensively studied class of DNAzymes are RNA-cleaving types which have been used to detect different metal ions and designing therapeutic agents. Several metal-specific DNAzymes have been reported including the GR-5 DNAzyme (lead-specific),[161] the CA1-3 DNAzymes (copper-specific),[163] the 39E DNAzyme (uranyl-specific) and the NaA43 DNAzyme (sodium-specific).[164] The NaA43 DNAzyme, which is reported to be more than 10,000-fold selective for sodium over other metal ions, was used to make a real-time sodium sensor in living cells.

Bioinformatics involves the development of techniques to store, data mine, search and manipulate biological data, including DNA nucleic acid sequence data. These have led to widely applied advances in computer science, especially string searching algorithms, machine learning and database theory.[165] String searching or matching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, were developed to search for specific sequences of nucleotides.[166] The DNA sequence may be aligned with other DNA sequences to identify homologous sequences and locate the specific mutations that make them distinct. These techniques, especially multiple sequence alignment, are used in studying phylogenetic relationships and protein function.[167] Data sets representing entire genomes' worth of DNA sequences, such as those produced by the Human Genome Project, are difficult to use without the annotations that identify the locations of genes and regulatory elements on each chromosome. Regions of DNA sequence that have the characteristic patterns associated with protein- or RNA-coding genes can be identified by gene finding algorithms, which allow researchers to predict the presence of particular gene products and their possible functions in an organism even before they have been isolated experimentally.[168] Entire genomes may also be compared, which can shed light on the evolutionary history of particular organism and permit the examination of complex evolutionary events.

DNA nanotechnology uses the unique molecular recognition properties of DNA and other nucleic acids to create self-assembling branched DNA complexes with useful properties.[169] DNA is thus used as a structural material rather than as a carrier of biological information. This has led to the creation of two-dimensional periodic lattices (both tile-based and using the DNA origami method) and three-dimensional structures in the shapes of polyhedra.[170]Nanomechanical devices and algorithmic self-assembly have also been demonstrated,[171] and these DNA structures have been used to template the arrangement of other molecules such as gold nanoparticles and streptavidin proteins.[172]

Because DNA collects mutations over time, which are then inherited, it contains historical information, and, by comparing DNA sequences, geneticists can infer the evolutionary history of organisms, their phylogeny.[173] This field of phylogenetics is a powerful tool in evolutionary biology. If DNA sequences within a species are compared, population geneticists can learn the history of particular populations. This can be used in studies ranging from ecological genetics to anthropology; For example, DNA evidence is being used to try to identify the Ten Lost Tribes of Israel.[174][175]

In a paper published in Nature in January 2013, scientists from the European Bioinformatics Institute and Agilent Technologies proposed a mechanism to use DNA's ability to code information as a means of digital data storage. The group was able to encode 739 kilobytes of data into DNA code, synthesize the actual DNA, then sequence the DNA and decode the information back to its original form, with a reported 100% accuracy. The encoded information consisted of text files and audio files. A prior experiment was published in August 2012. It was conducted by researchers at Harvard University, where the text of a 54,000-word book was encoded in DNA.[176][177]

DNA was first isolated by the Swiss physician Friedrich Miescher who, in 1869, discovered a microscopic substance in the pus of discarded surgical bandages. As it resided in the nuclei of cells, he called it "nuclein".[178][179] In 1878, Albrecht Kossel isolated the non-protein component of "nuclein", nucleic acid, and later isolated its five primary nucleobases.[180][181] In 1919, Phoebus Levene identified the base, sugar and phosphate nucleotide unit.[182] Levene suggested that DNA consisted of a string of nucleotide units linked together through the phosphate groups. Levene thought the chain was short and the bases repeated in a fixed order. In 1937, William Astbury produced the first X-ray diffraction patterns that showed that DNA had a regular structure.[183]

In 1927, Nikolai Koltsov proposed that inherited traits would be inherited via a "giant hereditary molecule" made up of "two mirror strands that would replicate in a semi-conservative fashion using each strand as a template".[184][185] In 1928, Frederick Griffith in his experiment discovered that traits of the "smooth" form of Pneumococcus could be transferred to the "rough" form of the same bacteria by mixing killed "smooth" bacteria with the live "rough" form.[186][187] This system provided the first clear suggestion that DNA carries genetic informationthe AveryMacLeodMcCarty experimentwhen Oswald Avery, along with coworkers Colin MacLeod and Maclyn McCarty, identified DNA as the transforming principle in 1943.[188] DNA's role in heredity was confirmed in 1952, when Alfred Hershey and Martha Chase in the HersheyChase experiment showed that DNA is the genetic material of the T2 phage.[189]

In 1953, James Watson and Francis Crick suggested what is now accepted as the first correct double-helix model of DNA structure in the journal Nature.[11] Their double-helix, molecular model of DNA was then based on one X-ray diffraction image (labeled as "Photo 51")[190] taken by Rosalind Franklin and Raymond Gosling in May 1952, and the information that the DNA bases are paired.

Experimental evidence supporting the Watson and Crick model was published in a series of five articles in the same issue of Nature.[191] Of these, Franklin and Gosling's paper was the first publication of their own X-ray diffraction data and original analysis method that partly supported the Watson and Crick model;[50][192] this issue also contained an article on DNA structure by Maurice Wilkins and two of his colleagues, whose analysis and in vivo B-DNA X-ray patterns also supported the presence in vivo of the double-helical DNA configurations as proposed by Crick and Watson for their double-helix molecular model of DNA in the prior two pages of Nature.[51] In 1962, after Franklin's death, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine.[193] Nobel Prizes are awarded only to living recipients. A debate continues about who should receive credit for the discovery.[194]

In an influential presentation in 1957, Crick laid out the central dogma of molecular biology, which foretold the relationship between DNA, RNA, and proteins, and articulated the "adaptor hypothesis".[195] Final confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 through the MeselsonStahl experiment.[196] Further work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of bases, called codons, allowing Har Gobind Khorana, Robert W. Holley and Marshall Warren Nirenberg to decipher the genetic code.[197] These findings represent the birth of molecular biology.

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DNA - Wikipedia

Gene therapy is the therapeutic delivery of nucleic acid polymers into a patient's cells as a drug to treat disease.[1] The first attempt at modifying human DNA was performed in 1980 by Martin Cline, but the first successful and approved[by whom?] nuclear gene transfer in humans was performed in May 1989.[2] The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990.

Between 1989 and February 2016, over 2,300 clinical trials had been conducted, more than half of them in phase I.[3]

It should be noted that not all medical procedures that introduce alterations to a patient's genetic makeup can be considered gene therapy. Bone marrow transplantation and organ transplants in general have been found to introduce foreign DNA into patients.[4] Gene therapy is defined by the precision of the procedure and the intention of direct therapeutic effects.

Gene therapy was conceptualized in 1972, by authors who urged caution before commencing human gene therapy studies.

The first attempt, an unsuccessful one, at gene therapy (as well as the first case of medical transfer of foreign genes into humans not counting organ transplantation) was performed by Martin Cline on 10 July 1980.[5][6] Cline claimed that one of the genes in his patients was active six months later, though he never published this data or had it verified[7] and even if he is correct, it's unlikely it produced any significant beneficial effects treating beta-thalassemia.[8]

After extensive research on animals throughout the 1980s and a 1989 bacterial gene tagging trial on humans, the first gene therapy widely accepted as a success was demonstrated in a trial that started on September 14, 1990, when Ashi DeSilva was treated for ADA-SCID.[9]

The first somatic treatment that produced a permanent genetic change was performed in 1993.[10]

This procedure was referred to sensationally and somewhat inaccurately in the media as a "three parent baby", though mtDNA is not the primary human genome and has little effect on an organism's individual characteristics beyond powering their cells.

Gene therapy is a way to fix a genetic problem at its source. The polymers are either translated into proteins, interfere with target gene expression, or possibly correct genetic mutations.

The most common form uses DNA that encodes a functional, therapeutic gene to replace a mutated gene. The polymer molecule is packaged within a "vector", which carries the molecule inside cells.

Early clinical failures led to dismissals of gene therapy. Clinical successes since 2006 regained researchers' attention, although as of 2014, it was still largely an experimental technique.[11] These include treatment of retinal diseases Leber's congenital amaurosis[12][13][14][15] and choroideremia,[16]X-linked SCID,[17] ADA-SCID,[18][19]adrenoleukodystrophy,[20]chronic lymphocytic leukemia (CLL),[21]acute lymphocytic leukemia (ALL),[22]multiple myeloma,[23]haemophilia[19] and Parkinson's disease.[24] Between 2013 and April 2014, US companies invested over $600 million in the field.[25]

The first commercial gene therapy, Gendicine, was approved in China in 2003 for the treatment of certain cancers.[26] In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia.[27] In 2012 Glybera, a treatment for a rare inherited disorder, became the first treatment to be approved for clinical use in either Europe or the United States after its endorsement by the European Commission.[11][28]

Following early advances in genetic engineering of bacteria, cells, and small animals, scientists started considering how to apply it to medicine. Two main approaches were considered replacing or disrupting defective genes.[29] Scientists focused on diseases caused by single-gene defects, such as cystic fibrosis, haemophilia, muscular dystrophy, thalassemia and sickle cell anemia. Glybera treats one such disease, caused by a defect in lipoprotein lipase.[28]

DNA must be administered, reach the damaged cells, enter the cell and express/disrupt a protein.[30] Multiple delivery techniques have been explored. The initial approach incorporated DNA into an engineered virus to deliver the DNA into a chromosome.[31][32]Naked DNA approaches have also been explored, especially in the context of vaccine development.[33]

Generally, efforts focused on administering a gene that causes a needed protein to be expressed. More recently, increased understanding of nuclease function has led to more direct DNA editing, using techniques such as zinc finger nucleases and CRISPR. The vector incorporates genes into chromosomes. The expressed nucleases then knock out and replace genes in the chromosome. As of 2014 these approaches involve removing cells from patients, editing a chromosome and returning the transformed cells to patients.[34]

Gene editing is a potential approach to alter the human genome to treat genetic diseases,[35] viral diseases,[36] and cancer.[37] As of 2016 these approaches were still years from being medicine.[38][39]

Gene therapy may be classified into two types:

In somatic cell gene therapy (SCGT), the therapeutic genes are transferred into any cell other than a gamete, germ cell, gametocyte or undifferentiated stem cell. Any such modifications affect the individual patient only, and are not inherited by offspring. Somatic gene therapy represents mainstream basic and clinical research, in which therapeutic DNA (either integrated in the genome or as an external episome or plasmid) is used to treat disease.

Over 600 clinical trials utilizing SCGT are underway in the US. Most focus on severe genetic disorders, including immunodeficiencies, haemophilia, thalassaemia and cystic fibrosis. Such single gene disorders are good candidates for somatic cell therapy. The complete correction of a genetic disorder or the replacement of multiple genes is not yet possible. Only a few of the trials are in the advanced stages.[40]

In germline gene therapy (GGT), germ cells (sperm or eggs) are modified by the introduction of functional genes into their genomes. Modifying a germ cell causes all the organism's cells to contain the modified gene. The change is therefore heritable and passed on to later generations. Australia, Canada, Germany, Israel, Switzerland and the Netherlands[41] prohibit GGT for application in human beings, for technical and ethical reasons, including insufficient knowledge about possible risks to future generations[41] and higher risks versus SCGT.[42] The US has no federal controls specifically addressing human genetic modification (beyond FDA regulations for therapies in general).[41][43][44][45]

The delivery of DNA into cells can be accomplished by multiple methods. The two major classes are recombinant viruses (sometimes called biological nanoparticles or viral vectors) and naked DNA or DNA complexes (non-viral methods).

In order to replicate, viruses introduce their genetic material into the host cell, tricking the host's cellular machinery into using it as blueprints for viral proteins. Scientists exploit this by substituting a virus's genetic material with therapeutic DNA. (The term 'DNA' may be an oversimplification, as some viruses contain RNA, and gene therapy could take this form as well.) A number of viruses have been used for human gene therapy, including retrovirus, adenovirus, lentivirus, herpes simplex, vaccinia and adeno-associated virus.[3] Like the genetic material (DNA or RNA) in viruses, therapeutic DNA can be designed to simply serve as a temporary blueprint that is degraded naturally or (at least theoretically) to enter the host's genome, becoming a permanent part of the host's DNA in infected cells.

Non-viral methods present certain advantages over viral methods, such as large scale production and low host immunogenicity. However, non-viral methods initially produced lower levels of transfection and gene expression, and thus lower therapeutic efficacy. Later technology remedied this deficiency[citation needed].

Methods for non-viral gene therapy include the injection of naked DNA, electroporation, the gene gun, sonoporation, magnetofection, the use of oligonucleotides, lipoplexes, dendrimers, and inorganic nanoparticles.

Some of the unsolved problems include:

Three patients' deaths have been reported in gene therapy trials, putting the field under close scrutiny. The first was that of Jesse Gelsinger in 1999.[52] One X-SCID patient died of leukemia in 2003.[9] In 2007, a rheumatoid arthritis patient died from an infection; the subsequent investigation concluded that the death was not related to gene therapy.[53]

In 1972 Friedmann and Roblin authored a paper in Science titled "Gene therapy for human genetic disease?"[54] Rogers (1970) was cited for proposing that exogenous good DNA be used to replace the defective DNA in those who suffer from genetic defects.[55]

In 1984 a retrovirus vector system was designed that could efficiently insert foreign genes into mammalian chromosomes.[56]

The first approved gene therapy clinical research in the US took place on 14 September 1990, at the National Institutes of Health (NIH), under the direction of William French Anderson.[57] Four-year-old Ashanti DeSilva received treatment for a genetic defect that left her with ADA-SCID, a severe immune system deficiency. The effects were temporary, but successful.[58]

Cancer gene therapy was introduced in 1992/93 (Trojan et al. 1993).[59] The treatment of glioblastoma multiforme, the malignant brain tumor whose outcome is always fatal, was done using a vector expressing antisense IGF-I RNA (clinical trial approved by NIH n 1602, and FDA in 1994). This therapy also represents the beginning of cancer immunogene therapy, a treatment which proves to be effective due to the anti-tumor mechanism of IGF-I antisense, which is related to strong immune and apoptotic phenomena.

In 1992 Claudio Bordignon, working at the Vita-Salute San Raffaele University, performed the first gene therapy procedure using hematopoietic stem cells as vectors to deliver genes intended to correct hereditary diseases.[60] In 2002 this work led to the publication of the first successful gene therapy treatment for adenosine deaminase-deficiency (SCID). The success of a multi-center trial for treating children with SCID (severe combined immune deficiency or "bubble boy" disease) from 2000 and 2002, was questioned when two of the ten children treated at the trial's Paris center developed a leukemia-like condition. Clinical trials were halted temporarily in 2002, but resumed after regulatory review of the protocol in the US, the United Kingdom, France, Italy and Germany.[61]

In 1993 Andrew Gobea was born with SCID following prenatal genetic screening. Blood was removed from his mother's placenta and umbilical cord immediately after birth, to acquire stem cells. The allele that codes for adenosine deaminase (ADA) was obtained and inserted into a retrovirus. Retroviruses and stem cells were mixed, after which the viruses inserted the gene into the stem cell chromosomes. Stem cells containing the working ADA gene were injected into Andrew's blood. Injections of the ADA enzyme were also given weekly. For four years T cells (white blood cells), produced by stem cells, made ADA enzymes using the ADA gene. After four years more treatment was needed.[citation needed]

Jesse Gelsinger's death in 1999 impeded gene therapy research in the US.[62][63] As a result, the FDA suspended several clinical trials pending the reevaluation of ethical and procedural practices.[64]

The modified cancer gene therapy strategy of antisense IGF-I RNA (NIH n 1602)[65] using antisense / triple helix anti IGF-I approach was registered in 2002 by Wiley gene therapy clinical trial - n 635 and 636. The approach has shown promising results in the treatment of six different malignant tumors: glioblastoma, cancers of liver, colon, prostate, uterus and ovary (Collaborative NATO Science Programme on Gene Therapy USA, France, Poland n LST 980517 conducted by J. Trojan) (Trojan et al., 2012). This antigene antisense/triple helix therapy has proven to be efficient, due to the mechanism stopping simultaneously IGF-I expression on translation and transcription levels, strengthening anti-tumor immune and apoptotic phenomena.

Sickle-cell disease can be treated in mice.[66] The mice which have essentially the same defect that causes human cases used a viral vector to induce production of fetal hemoglobin (HbF), which normally ceases to be produced shortly after birth. In humans, the use of hydroxyurea to stimulate the production of HbF temporarily alleviates sickle cell symptoms. The researchers demonstrated this treatment to be a more permanent means to increase therapeutic HbF production.[67]

A new gene therapy approach repaired errors in messenger RNA derived from defective genes. This technique has the potential to treat thalassaemia, cystic fibrosis and some cancers.[68]

Researchers created liposomes 25 nanometers across that can carry therapeutic DNA through pores in the nuclear membrane.[69]

In 2003 a research team inserted genes into the brain for the first time. They used liposomes coated in a polymer called polyethylene glycol, which, unlike viral vectors, are small enough to cross the bloodbrain barrier.[70]

Short pieces of double-stranded RNA (short, interfering RNAs or siRNAs) are used by cells to degrade RNA of a particular sequence. If a siRNA is designed to match the RNA copied from a faulty gene, then the abnormal protein product of that gene will not be produced.[71]

Gendicine is a cancer gene therapy that delivers the tumor suppressor gene p53 using an engineered adenovirus. In 2003, it was approved in China for the treatment of head and neck squamous cell carcinoma.[26]

In March researchers announced the successful use of gene therapy to treat two adult patients for X-linked chronic granulomatous disease, a disease which affects myeloid cells and damages the immune system. The study is the first to show that gene therapy can treat the myeloid system.[72]

In May a team reported a way to prevent the immune system from rejecting a newly delivered gene.[73] Similar to organ transplantation, gene therapy has been plagued by this problem. The immune system normally recognizes the new gene as foreign and rejects the cells carrying it. The research utilized a newly uncovered network of genes regulated by molecules known as microRNAs. This natural function selectively obscured their therapeutic gene in immune system cells and protected it from discovery. Mice infected with the gene containing an immune-cell microRNA target sequence did not reject the gene.

In August scientists successfully treated metastatic melanoma in two patients using killer T cells genetically retargeted to attack the cancer cells.[74]

In November researchers reported on the use of VRX496, a gene-based immunotherapy for the treatment of HIV that uses a lentiviral vector to deliver an antisense gene against the HIV envelope. In a phase I clinical trial, five subjects with chronic HIV infection who had failed to respond to at least two antiretroviral regimens were treated. A single intravenous infusion of autologous CD4 T cells genetically modified with VRX496 was well tolerated. All patients had stable or decreased viral load; four of the five patients had stable or increased CD4 T cell counts. All five patients had stable or increased immune response to HIV antigens and other pathogens. This was the first evaluation of a lentiviral vector administered in a US human clinical trial.[75][76]

In May researchers announced the first gene therapy trial for inherited retinal disease. The first operation was carried out on a 23-year-old British male, Robert Johnson, in early 2007.[77]

Leber's congenital amaurosis is an inherited blinding disease caused by mutations in the RPE65 gene. The results of a small clinical trial in children were published in April.[12] Delivery of recombinant adeno-associated virus (AAV) carrying RPE65 yielded positive results. In May two more groups reported positive results in independent clinical trials using gene therapy to treat the condition. In all three clinical trials, patients recovered functional vision without apparent side-effects.[12][13][14][15]

In September researchers were able to give trichromatic vision to squirrel monkeys.[78] In November 2009, researchers halted a fatal genetic disorder called adrenoleukodystrophy in two children using a lentivirus vector to deliver a functioning version of ABCD1, the gene that is mutated in the disorder.[79]

An April paper reported that gene therapy addressed achromatopsia (color blindness) in dogs by targeting cone photoreceptors. Cone function and day vision were restored for at least 33 months in two young specimens. The therapy was less efficient for older dogs.[80]

In September it was announced that an 18-year-old male patient in France with beta-thalassemia major had been successfully treated.[81] Beta-thalassemia major is an inherited blood disease in which beta haemoglobin is missing and patients are dependent on regular lifelong blood transfusions.[82] The technique used a lentiviral vector to transduce the human -globin gene into purified blood and marrow cells obtained from the patient in June 2007.[83] The patient's haemoglobin levels were stable at 9 to 10 g/dL. About a third of the hemoglobin contained the form introduced by the viral vector and blood transfusions were not needed.[83][84] Further clinical trials were planned.[85]Bone marrow transplants are the only cure for thalassemia, but 75% of patients do not find a matching donor.[84]

Cancer immunogene therapy using modified anti gene, antisense / triple helix approach was introduced in South America in 2010/11 in La Sabana University, Bogota (Ethical Committee 14.12.2010, no P-004-10). Considering the ethical aspect of gene diagnostic and gene therapy targeting IGF-I, the IGF-I expressing tumors i.e. lung and epidermis cancers, were treated (Trojan et al. 2016). [86][87]

In 2007 and 2008, a man was cured of HIV by repeated Hematopoietic stem cell transplantation (see also Allogeneic stem cell transplantation, Allogeneic bone marrow transplantation, Allotransplantation) with double-delta-32 mutation which disables the CCR5 receptor. This cure was accepted by the medical community in 2011.[88] It required complete ablation of existing bone marrow, which is very debilitating.

In August two of three subjects of a pilot study were confirmed to have been cured from chronic lymphocytic leukemia (CLL). The therapy used genetically modified T cells to attack cells that expressed the CD19 protein to fight the disease.[21] In 2013, the researchers announced that 26 of 59 patients had achieved complete remission and the original patient had remained tumor-free.[89]

Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for coronary artery disease as well as treatment for the damage that occurs to the heart after myocardial infarction.[90][91]

In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia; it delivers the gene encoding for VEGF.[92][27] Neovasculogen is a plasmid encoding the CMV promoter and the 165 amino acid form of VEGF.[93][94]

The FDA approved Phase 1 clinical trials on thalassemia major patients in the US for 10 participants in July.[95] The study was expected to continue until 2015.[96]

In July 2012, the European Medicines Agency recommended approval of a gene therapy treatment for the first time in either Europe or the United States. The treatment used Alipogene tiparvovec (Glybera) to compensate for lipoprotein lipase deficiency, which can cause severe pancreatitis.[97] The recommendation was endorsed by the European Commission in November 2012[11][28][98][99] and commercial rollout began in late 2014.[100]

In December 2012, it was reported that 10 of 13 patients with multiple myeloma were in remission "or very close to it" three months after being injected with a treatment involving genetically engineered T cells to target proteins NY-ESO-1 and LAGE-1, which exist only on cancerous myeloma cells.[23]

In March researchers reported that three of five subjects who had acute lymphocytic leukemia (ALL) had been in remission for five months to two years after being treated with genetically modified T cells which attacked cells with CD19 genes on their surface, i.e. all B-cells, cancerous or not. The researchers believed that the patients' immune systems would make normal T-cells and B-cells after a couple of months. They were also given bone marrow. One patient relapsed and died and one died of a blood clot unrelated to the disease.[22]

Following encouraging Phase 1 trials, in April, researchers announced they were starting Phase 2 clinical trials (called CUPID2 and SERCA-LVAD) on 250 patients[101] at several hospitals to combat heart disease. The therapy was designed to increase the levels of SERCA2, a protein in heart muscles, improving muscle function.[102] The FDA granted this a Breakthrough Therapy Designation to accelerate the trial and approval process.[103] In 2016 it was reported that no improvement was found from the CUPID 2 trial.[104]

In July researchers reported promising results for six children with two severe hereditary diseases had been treated with a partially deactivated lentivirus to replace a faulty gene and after 732 months. Three of the children had metachromatic leukodystrophy, which causes children to lose cognitive and motor skills.[105] The other children had Wiskott-Aldrich syndrome, which leaves them to open to infection, autoimmune diseases and cancer.[106] Follow up trials with gene therapy on another six children with Wiskott-Aldrich syndrome were also reported as promising.[107][108]

In October researchers reported that two children born with adenosine deaminase severe combined immunodeficiency disease (ADA-SCID) had been treated with genetically engineered stem cells 18 months previously and that their immune systems were showing signs of full recovery. Another three children were making progress.[19] In 2014 a further 18 children with ADA-SCID were cured by gene therapy.[109] ADA-SCID children have no functioning immune system and are sometimes known as "bubble children."[19]

Also in October researchers reported that they had treated six haemophilia sufferers in early 2011 using an adeno-associated virus. Over two years later all six were producing clotting factor.[19][110]

Data from three trials on Topical cystic fibrosis transmembrane conductance regulator gene therapy were reported to not support its clinical use as a mist inhaled into the lungs to treat cystic fibrosis patients with lung infections.[111]

In January researchers reported that six choroideremia patients had been treated with adeno-associated virus with a copy of REP1. Over a six-month to two-year period all had improved their sight.[112][113] By 2016, 32 patients had been treated with positive results and researchers were hopeful the treatment would be long-lasting.[16] Choroideremia is an inherited genetic eye disease with no approved treatment, leading to loss of sight.

In March researchers reported that 12 HIV patients had been treated since 2009 in a trial with a genetically engineered virus with a rare mutation (CCR5 deficiency) known to protect against HIV with promising results.[114][115]

Clinical trials of gene therapy for sickle cell disease were started in 2014[116][117] although one review failed to find any such trials.[118]

In February LentiGlobin BB305, a gene therapy treatment undergoing clinical trials for treatment of beta thalassemia gained FDA "breakthrough" status after several patients were able to forgo the frequent blood transfusions usually required to treat the disease.[119]

In March researchers delivered a recombinant gene encoding a broadly neutralizing antibody into monkeys infected with simian HIV; the monkeys' cells produced the antibody, which cleared them of HIV. The technique is named immunoprophylaxis by gene transfer (IGT). Animal tests for antibodies to ebola, malaria, influenza and hepatitis are underway.[120][121]

In March scientists, including an inventor of CRISPR, urged a worldwide moratorium on germline gene therapy, writing scientists should avoid even attempting, in lax jurisdictions, germline genome modification for clinical application in humans until the full implications are discussed among scientific and governmental organizations.[122][123][124][125]

Also in 2015 Glybera was approved for the German market.[126]

In October, researchers announced that they had treated a baby girl, Layla Richards, with an experimental treatment using donor T-cells genetically engineered to attack cancer cells. Two months after the treatment she was still free of her cancer (a highly aggressive form of acute lymphoblastic leukaemia [ALL]). Children with highly aggressive ALL normally have a very poor prognosis and Layla's disease had been regarded as terminal before the treatment.[127]

In December, scientists of major world academies called for a moratorium on inheritable human genome edits, including those related to CRISPR-Cas9 technologies[128] but that basic research including embryo gene editing should continue.[129]

In April the Committee for Medicinal Products for Human Use of the European Medicines Agency endorsed a gene therapy treatment called Strimvelis and recommended it be approved.[130][131] This treats children born with ADA-SCID and who have no functioning immune system - sometimes called the "bubble baby" disease. This would be the second gene therapy treatment to be approved in Europe.[132]

Speculated uses for gene therapy include:

Gene Therapy techniques have the potential to provide alternative treatments for those with infertility. Recently, successful experimentation on mice has proven that fertility can be restored by using the gene therapy method, CRISPR.[133] Spermatogenical stem cells from another organism were transplanted into the testes of an infertile male mouse. The stem cells re-established spermatogenesis and fertility.[134]

Athletes might adopt gene therapy technologies to improve their performance.[135]Gene doping is not known to occur, but multiple gene therapies may have such effects. Kayser et al. argue that gene doping could level the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic/enhancement purposes compromises the ethical foundations of medicine and sports.[136]

Genetic engineering could be used to change physical appearance, metabolism, and even improve physical capabilities and mental faculties such as memory and intelligence. Ethical claims about germline engineering include beliefs that every fetus has a right to remain genetically unmodified, that parents hold the right to genetically modify their offspring, and that every child has the right to be born free of preventable diseases.[137][138][139] For adults, genetic engineering could be seen as another enhancement technique to add to diet, exercise, education, cosmetics and plastic surgery.[140][141] Another theorist claims that moral concerns limit but do not prohibit germline engineering.[142]

Possible regulatory schemes include a complete ban, provision to everyone, or professional self-regulation. The American Medical Associations Council on Ethical and Judicial Affairs stated that "genetic interventions to enhance traits should be considered permissible only in severely restricted situations: (1) clear and meaningful benefits to the fetus or child; (2) no trade-off with other characteristics or traits; and (3) equal access to the genetic technology, irrespective of income or other socioeconomic characteristics."[143]

As early in the history of biotechnology as 1990, there have been scientists opposed to attempts to modify the human germline using these new tools,[144] and such concerns have continued as technology progressed.[145] With the advent of new techniques like CRISPR, in March 2015 a group of scientists urged a worldwide moratorium on clinical use of gene editing technologies to edit the human genome in a way that can be inherited.[122][123][124][125] In April 2015, researchers sparked controversy when they reported results of basic research to edit the DNA of non-viable human embryos using CRISPR.[133][146]

Regulations covering genetic modification are part of general guidelines about human-involved biomedical research.

The Helsinki Declaration (Ethical Principles for Medical Research Involving Human Subjects) was amended by the World Medical Association's General Assembly in 2008. This document provides principles physicians and researchers must consider when involving humans as research subjects. The Statement on Gene Therapy Research initiated by the Human Genome Organization (HUGO) in 2001 provides a legal baseline for all countries. HUGOs document emphasizes human freedom and adherence to human rights, and offers recommendations for somatic gene therapy, including the importance of recognizing public concerns about such research.[147]

No federal legislation lays out protocols or restrictions about human genetic engineering. This subject is governed by overlapping regulations from local and federal agencies, including the Department of Health and Human Services, the FDA and NIH's Recombinant DNA Advisory Committee. Researchers seeking federal funds for an investigational new drug application, (commonly the case for somatic human genetic engineering), must obey international and federal guidelines for the protection of human subjects.[148]

NIH serves as the main gene therapy regulator for federally funded research. Privately funded research is advised to follow these regulations. NIH provides funding for research that develops or enhances genetic engineering techniques and to evaluate the ethics and quality in current research. The NIH maintains a mandatory registry of human genetic engineering research protocols that includes all federally funded projects.

An NIH advisory committee published a set of guidelines on gene manipulation.[149] The guidelines discuss lab safety as well as human test subjects and various experimental types that involve genetic changes. Several sections specifically pertain to human genetic engineering, including Section III-C-1. This section describes required review processes and other aspects when seeking approval to begin clinical research involving genetic transfer into a human patient.[150] The protocol for a gene therapy clinical trial must be approved by the NIH's Recombinant DNA Advisory Committee prior to any clinical trial beginning; this is different from any other kind of clinical trial.[149]

As with other kinds of drugs, the FDA regulates the quality and safety of gene therapy products and supervises how these products are used clinically. Therapeutic alteration of the human genome falls under the same regulatory requirements as any other medical treatment. Research involving human subjects, such as clinical trials, must be reviewed and approved by the FDA and an Institutional Review Board.[151][152]

Gene therapy is the basis for the plotline of the film I Am Legend[153] and the TV show Will Gene Therapy Change the Human Race?.[154]

Read more:
Gene therapy - Wikipedia

Diabetes mellitus (DM), commonly referred to as diabetes, is a group of metabolic diseases in which there are high blood sugar levels over a prolonged period.[2] Symptoms of high blood sugar include frequent urination, increased thirst, and increased hunger. If left untreated, diabetes can cause many complications.[3]Acute complications can include diabetic ketoacidosis, nonketotic hyperosmolar coma, or death.[4] Serious long-term complications include heart disease, stroke, chronic kidney failure, foot ulcers, and damage to the eyes.[3]

Diabetes is due to either the pancreas not producing enough insulin or the cells of the body not responding properly to the insulin produced.[5] There are three main types of diabetes mellitus:

Prevention and treatment involve maintaining a healthy diet, regular physical exercise, a normal body weight, and avoiding use of tobacco. Control of blood pressure and maintaining proper foot care are important for people with the disease. Type 1 DM must be managed with insulin injections.[3] Type 2 DM may be treated with medications with or without insulin.[7] Insulin and some oral medications can cause low blood sugar.[8]Weight loss surgery in those with obesity is sometimes an effective measure in those with type 2 DM.[9] Gestational diabetes usually resolves after the birth of the baby.[10]

As of 2015[update], an estimated 415 million people had diabetes worldwide,[11] with type 2 DM making up about 90% of the cases.[12][13] This represents 8.3% of the adult population,[13] with equal rates in both women and men.[14] As of 2014[update], trends suggested the rate would continue to rise.[15] Diabetes at least doubles a person's risk of early death.[3] From 2012 to 2015, approximately 1.5 to 5.0 million deaths each year resulted from diabetes.[7][11] The global economic cost of diabetes in 2014 was estimated to be US$612 billion.[16] In the United States, diabetes cost $245 billion in 2012.[17]

The classic symptoms of untreated diabetes are weight loss, polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger).[18] Symptoms may develop rapidly (weeks or months) in type1 DM, while they usually develop much more slowly and may be subtle or absent in type2 DM.

Several other signs and symptoms can mark the onset of diabetes although they are not specific to the disease. In addition to the known ones above, they include blurry vision, headache, fatigue, slow healing of cuts, and itchy skin. Prolonged high blood glucose can cause glucose absorption in the lens of the eye, which leads to changes in its shape, resulting in vision changes. A number of skin rashes that can occur in diabetes are collectively known as diabetic dermadromes.

Low blood sugar is common in persons with type 1 and type 2 DM. Most cases are mild and are not considered medical emergencies. Effects can range from feelings of unease, sweating, trembling, and increased appetite in mild cases to more serious issues such as confusion, changes in behavior such as aggressiveness, seizures, unconsciousness, and (rarely) permanent brain damage or death in severe cases.[19][20] Moderate hypoglycemia may easily be mistaken for drunkenness;[21] rapid breathing and sweating, cold, pale skin are characteristic of hypoglycemia but not definitive.[22] Mild to moderate cases are self-treated by eating or drinking something high in sugar. Severe cases can lead to unconsciousness and must be treated with intravenous glucose or injections with glucagon.

People (usually with type1 DM) may also experience episodes of diabetic ketoacidosis, a metabolic disturbance characterized by nausea, vomiting and abdominal pain, the smell of acetone on the breath, deep breathing known as Kussmaul breathing, and in severe cases a decreased level of consciousness.[23]

A rare but equally severe possibility is hyperosmolar nonketotic state, which is more common in type2 DM and is mainly the result of dehydration.[23]

All forms of diabetes increase the risk of long-term complications. These typically develop after many years (1020), but may be the first symptom in those who have otherwise not received a diagnosis before that time.

The major long-term complications relate to damage to blood vessels. Diabetes doubles the risk of cardiovascular disease[24] and about 75% of deaths in diabetics are due to coronary artery disease.[25] Other "macrovascular" diseases are stroke, and peripheral vascular disease.

The primary complications of diabetes due to damage in small blood vessels include damage to the eyes, kidneys, and nerves.[26] Damage to the eyes, known as diabetic retinopathy, is caused by damage to the blood vessels in the retina of the eye, and can result in gradual vision loss and blindness.[26] Damage to the kidneys, known as diabetic nephropathy, can lead to tissue scarring, urine protein loss, and eventually chronic kidney disease, sometimes requiring dialysis or kidney transplant.[26] Damage to the nerves of the body, known as diabetic neuropathy, is the most common complication of diabetes.[26] The symptoms can include numbness, tingling, pain, and altered pain sensation, which can lead to damage to the skin. Diabetes-related foot problems (such as diabetic foot ulcers) may occur, and can be difficult to treat, occasionally requiring amputation. Additionally, proximal diabetic neuropathy causes painful muscle wasting and weakness.

There is a link between cognitive deficit and diabetes. Compared to those without diabetes, those with the disease have a 1.2 to 1.5-fold greater rate of decline in cognitive function.[27]

Diabetes mellitus is classified into four broad categories: type1, type2, gestational diabetes, and "other specific types".[5] The "other specific types" are a collection of a few dozen individual causes.[5] Diabetes is a more variable disease than once thought and people may have combinations of forms.[29] The term "diabetes", without qualification, usually refers to diabetes mellitus.

Type1 diabetes mellitus is characterized by loss of the insulin-producing beta cells of the islets of Langerhans in the pancreas, leading to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. The majority of type1 diabetes is of the immune-mediated nature, in which a T-cell-mediated autoimmune attack leads to the loss of beta cells and thus insulin.[30] It causes approximately 10% of diabetes mellitus cases in North America and Europe. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Type1 diabetes can affect children or adults, but was traditionally termed "juvenile diabetes" because a majority of these diabetes cases were in children.

"Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was traditionally used to describe the dramatic and recurrent swings in glucose levels, often occurring for no apparent reason in insulin-dependent diabetes. This term, however, has no biologic basis and should not be used.[31] Still, type1 diabetes can be accompanied by irregular and unpredictable high blood sugar levels, frequently with ketosis, and sometimes with serious low blood sugar levels. Other complications include an impaired counterregulatory response to low blood sugar, infection, gastroparesis (which leads to erratic absorption of dietary carbohydrates), and endocrinopathies (e.g., Addison's disease).[31] These phenomena are believed to occur no more frequently than in 1% to 2% of persons with type1 diabetes.[32]

Type1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes, known to influence the risk of diabetes. The increase of incidence of type 1 diabetes reflects the modern lifestyle.[33] In genetically susceptible people, the onset of diabetes can be triggered by one or more environmental factors,[34] such as a viral infection or diet. Several viruses have been implicated, but to date there is no stringent evidence to support this hypothesis in humans.[34][35] Among dietary factors, data suggest that gliadin (a protein present in gluten) may play a role in the development of type 1 diabetes, but the mechanism is not fully understood.[36][37]

Type2 DM is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion.[5] The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Diabetes mellitus cases due to a known defect are classified separately. Type2 DM is the most common type of diabetes mellitus.

In the early stage of type2, the predominant abnormality is reduced insulin sensitivity. At this stage, high blood sugar can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce the liver's glucose production.

Type2 DM is due primarily to lifestyle factors and genetics.[38] A number of lifestyle factors are known to be important to the development of type2 DM, including obesity (defined by a body mass index of greater than 30), lack of physical activity, poor diet, stress, and urbanization.[12] Excess body fat is associated with 30% of cases in those of Chinese and Japanese descent, 6080% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders.[5] Even those who are not obese often have a high waisthip ratio.[5]

Dietary factors also influence the risk of developing type2 DM. Consumption of sugar-sweetened drinks in excess is associated with an increased risk.[39][40] The type of fats in the diet is also important, with saturated fats and trans fatty acids increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk.[38] Eating lots of white rice also may increase the risk of diabetes.[41] A lack of exercise is believed to cause 7% of cases.[42]

Gestational diabetes mellitus (GDM) resembles type2 DM in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 210% of all pregnancies and may improve or disappear after delivery.[43] However, after pregnancy approximately 510% of women with gestational diabetes are found to have diabetes mellitus, most commonly type 2.[43] Gestational diabetes is fully treatable, but requires careful medical supervision throughout the pregnancy. Management may include dietary changes, blood glucose monitoring, and in some cases, insulin may be required.

Though it may be transient, untreated gestational diabetes can damage the health of the fetus or mother. Risks to the baby include macrosomia (high birth weight), congenital heart and central nervous system abnormalities, and skeletal muscle malformations. Increased levels of insulin in a fetus's blood may inhibit fetal surfactant production and cause respiratory distress syndrome. A high blood bilirubin level may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental perfusion due to vascular impairment. Labor induction may be indicated with decreased placental function. A Caesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.[citation needed]

Prediabetes indicates a condition that occurs when a person's blood glucose levels are higher than normal but not high enough for a diagnosis of type2 DM. Many people destined to develop type2 DM spend many years in a state of prediabetes.

Latent autoimmune diabetes of adults (LADA) is a condition in which type1 DM develops in adults. Adults with LADA are frequently initially misdiagnosed as having type2 DM, based on age rather than etiology.

Some cases of diabetes are caused by the body's tissue receptors not responding to insulin (even when insulin levels are normal, which is what separates it from type2 diabetes); this form is very uncommon. Genetic mutations (autosomal or mitochondrial) can lead to defects in beta cell function. Abnormal insulin action may also have been genetically determined in some cases. Any disease that causes extensive damage to the pancreas may lead to diabetes (for example, chronic pancreatitis and cystic fibrosis). Diseases associated with excessive secretion of insulin-antagonistic hormones can cause diabetes (which is typically resolved once the hormone excess is removed). Many drugs impair insulin secretion and some toxins damage pancreatic beta cells. The ICD-10 (1992) diagnostic entity, malnutrition-related diabetes mellitus (MRDM or MMDM, ICD-10 code E12), was deprecated by the World Health Organization when the current taxonomy was introduced in 1999.[44]

Other forms of diabetes mellitus include congenital diabetes, which is due to genetic defects of insulin secretion, cystic fibrosis-related diabetes, steroid diabetes induced by high doses of glucocorticoids, and several forms of monogenic diabetes.

"Type 3 diabetes" has been suggested as a term for Alzheimer's disease as the underlying processes may involve insulin resistance by the brain.[45]

The following is a comprehensive list of other causes of diabetes:[46]

Insulin is the principal hormone that regulates the uptake of glucose from the blood into most cells of the body, especially liver, muscle, and adipose tissue. Therefore, deficiency of insulin or the insensitivity of its receptors plays a central role in all forms of diabetes mellitus.[48]

The body obtains glucose from three main places: the intestinal absorption of food, the breakdown of glycogen, the storage form of glucose found in the liver, and gluconeogenesis, the generation of glucose from non-carbohydrate substrates in the body.[49] Insulin plays a critical role in balancing glucose levels in the body. Insulin can inhibit the breakdown of glycogen or the process of gluconeogenesis, it can stimulate the transport of glucose into fat and muscle cells, and it can stimulate the storage of glucose in the form of glycogen.[49]

Insulin is released into the blood by beta cells (-cells), found in the islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Insulin is used by about two-thirds of the body's cells to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage. Lower glucose levels result in decreased insulin release from the beta cells and in the breakdown of glycogen to glucose. This process is mainly controlled by the hormone glucagon, which acts in the opposite manner to insulin.[50]

If the amount of insulin available is insufficient, if cells respond poorly to the effects of insulin (insulin insensitivity or insulin resistance), or if the insulin itself is defective, then glucose will not be absorbed properly by the body cells that require it, and it will not be stored appropriately in the liver and muscles. The net effect is persistently high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as acidosis.[49]

When the glucose concentration in the blood remains high over time, the kidneys will reach a threshold of reabsorption, and glucose will be excreted in the urine (glycosuria).[51] This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production (polyuria) and increased fluid loss. Lost blood volume will be replaced osmotically from water held in body cells and other body compartments, causing dehydration and increased thirst (polydipsia).[49]

Diabetes mellitus is characterized by recurrent or persistent high blood sugar, and is diagnosed by demonstrating any one of the following:[44]

A positive result, in the absence of unequivocal high blood sugar, should be confirmed by a repeat of any of the above methods on a different day. It is preferable to measure a fasting glucose level because of the ease of measurement and the considerable time commitment of formal glucose tolerance testing, which takes two hours to complete and offers no prognostic advantage over the fasting test.[55] According to the current definition, two fasting glucose measurements above 126mg/dl (7.0mmol/l) is considered diagnostic for diabetes mellitus.

Per the World Health Organization people with fasting glucose levels from 6.1 to 6.9mmol/l (110 to 125mg/dl) are considered to have impaired fasting glucose.[56] people with plasma glucose at or above 7.8mmol/l (140mg/dl), but not over 11.1mmol/l (200mg/dl), two hours after a 75g oral glucose load are considered to have impaired glucose tolerance. Of these two prediabetic states, the latter in particular is a major risk factor for progression to full-blown diabetes mellitus, as well as cardiovascular disease.[57] The American Diabetes Association since 2003 uses a slightly different range for impaired fasting glucose of 5.6 to 6.9mmol/l (100 to 125mg/dl).[58]

Glycated hemoglobin is better than fasting glucose for determining risks of cardiovascular disease and death from any cause.[59]

The rare disease diabetes insipidus has similar symptoms to diabetes mellitus, but without disturbances in the sugar metabolism (insipidus means "without taste" in Latin) and does not involve the same disease mechanisms. Diabetes is a part of the wider condition known as metabolic syndrome.

There is no known preventive measure for type1 diabetes.[3] Type2 diabetes which accounts for 85-90% of all cases can often be prevented or delayed by maintaining a normal body weight, engaging in physical exercise, and consuming a healthful diet.[3] Higher levels of physical activity reduce the risk of diabetes by 28%.[60] Dietary changes known to be effective in helping to prevent diabetes include maintaining a diet rich in whole grains and fiber, and choosing good fats, such as the polyunsaturated fats found in nuts, vegetable oils, and fish.[61] Limiting sugary beverages and eating less red meat and other sources of saturated fat can also help prevent diabetes.[61] Tobacco smoking is also associated with an increased risk of diabetes and its complications, so smoking cessation can be an important preventive measure as well.[62]

The relationship between type 2 diabetes and the main modifiable risk factors (excess weight, unhealthy diet, physical inactivity and tobacco use) is similar in all regions of the world. There is growing evidence that the underlying determinants of diabetes are a reflection of the major forces driving social, economic and cultural change: globalization, urbanization, population ageing, and the general health policy environment.[63]

Diabetes mellitus is a chronic disease, for which there is no known cure except in very specific situations.[64] Management concentrates on keeping blood sugar levels as close to normal, without causing low blood sugar. This can usually be accomplished with a healthy diet, exercise, weight loss, and use of appropriate medications (insulin in the case of type1 diabetes; oral medications, as well as possibly insulin, in type2 diabetes).

Learning about the disease and actively participating in the treatment is important, since complications are far less common and less severe in people who have well-managed blood sugar levels.[65][66] The goal of treatment is an HbA1C level of 6.5%, but should not be lower than that, and may be set higher.[67] Attention is also paid to other health problems that may accelerate the negative effects of diabetes. These include smoking, elevated cholesterol levels, obesity, high blood pressure, and lack of regular exercise.[67]Specialized footwear is widely used to reduce the risk of ulceration, or re-ulceration, in at-risk diabetic feet. Evidence for the efficacy of this remains equivocal, however.[68]

People with diabetes can benefit from education about the disease and treatment, good nutrition to achieve a normal body weight, and exercise, with the goal of keeping both short-term and long-term blood glucose levels within acceptable bounds. In addition, given the associated higher risks of cardiovascular disease, lifestyle modifications are recommended to control blood pressure.[69]

Medications used to treat diabetes do so by lowering blood sugar levels. There are a number of different classes of anti-diabetic medications. Some are available by mouth, such as metformin, while others are only available by injection such as GLP-1 agonists. Type1 diabetes can only be treated with insulin, typically with a combination of regular and NPH insulin, or synthetic insulin analogs.[citation needed]

Metformin is generally recommended as a first line treatment for type2 diabetes, as there is good evidence that it decreases mortality.[70] It works by decreasing the liver's production of glucose.[71] Several other groups of drugs, mostly given by mouth, may also decrease blood sugar in type II DM. These include agents that increase insulin release, agents that decrease absorption of sugar from the intestines, and agents that make the body more sensitive to insulin.[71] When insulin is used in type2 diabetes, a long-acting formulation is usually added initially, while continuing oral medications.[70] Doses of insulin are then increased to effect.[70][72]

Since cardiovascular disease is a serious complication associated with diabetes, some have recommended blood pressure levels below 130/80mmHg.[73] However, evidence supports less than or equal to somewhere between 140/90mmHg to 160/100mmHg; the only additional benefit found for blood pressure targets beneath this range was an isolated decrease in stroke risk, and this was accompanied by an increased risk of other serious adverse events.[74][75] A 2016 review found potential harm to treating lower than 140 mmHg.[76] Among medications that lower blood pressure, angiotensin converting enzyme inhibitors (ACEIs) improve outcomes in those with DM while the similar medications angiotensin receptor blockers (ARBs) do not.[77]Aspirin is also recommended for people with cardiovascular problems, however routine use of aspirin has not been found to improve outcomes in uncomplicated diabetes.[78]

A pancreas transplant is occasionally considered for people with type1 diabetes who have severe complications of their disease, including end stage kidney disease requiring kidney transplantation.[79]

Weight loss surgery in those with obesity and type two diabetes is often an effective measure.[80] Many are able to maintain normal blood sugar levels with little or no medications following surgery[81] and long-term mortality is decreased.[82] There however is some short-term mortality risk of less than 1% from the surgery.[83] The body mass index cutoffs for when surgery is appropriate are not yet clear.[82] It is recommended that this option be considered in those who are unable to get both their weight and blood sugar under control.[84]

In countries using a general practitioner system, such as the United Kingdom, care may take place mainly outside hospitals, with hospital-based specialist care used only in case of complications, difficult blood sugar control, or research projects. In other circumstances, general practitioners and specialists share care in a team approach. Home telehealth support can be an effective management technique.[85]

no data

7.5

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1522.5

22.530

3037.5

37.545

4552.5

52.560

6067.5

67.575

7582.5

82.5

28-91

92-114

115-141

142-163

164-184

185-209

210-247

248-309

310-404

405-1879

As of 2016, 422 million people have diabetes worldwide,[86] up from an estimated 382 million people in 2013[13] and from 108 million in 1980.[86] Accounting for the shifting age structure of the global population, the prevalence of diabetes is 8.5% among adults, nearly double the rate of 4.7% in 1980.[86] Type2 makes up about 90% of the cases.[12][14] Some data indicate rates are roughly equal in women and men,[14] but male excess in diabetes has been found in many populations with higher type 2 incidence, possibly due to sex-related differences in insulin sensitivity, consequences of obesity and regional body fat deposition, and other contributing factors such as high blood pressure, tobacco smoking and alcohol intake.[87][88]

The World Health Organization (WHO) estimates that diabetes mellitus resulted in 1.5 million deaths in 2012, making it the 8th leading cause of death.[7][86] However another 2.2 million deaths worldwide were attributable to high blood glucose and the increased risks of cardiovascular disease and other associated complications (e.g. kidney failure), which often lead to premature death and are often listed as the underlying cause on death certificates rather than diabetes.[86][89] For example, in 2014, the International Diabetes Federation (IDF) estimated that diabetes resulted in 4.9 million deaths worldwide,[15] using modelling to estimate the total amount of deaths that could be directly or indirectly attributed to diabetes.[16]

Diabetes mellitus occurs throughout the world but is more common (especially type 2) in more developed countries. The greatest increase in rates has however been seen in low- and middle-income countries,[86] where more than 80% of diabetic deaths occur.[90] The fastest prevalence increase is expected to occur in Asia and Africa, where most people with diabetes will probably live in 2030.[91] The increase in rates in developing countries follows the trend of urbanization and lifestyle changes, including increasingly sedentary lifestyles, less physically demanding work and the global nutrition transition, marked by increased intake of foods that are high energy-dense but nutrient-poor (often high in sugar and saturated fats, sometimes referred to as the "Western-style" diet).[86][91]

Diabetes was one of the first diseases described,[92] with an Egyptian manuscript from c. 1500 BCE mentioning "too great emptying of the urine".[93] The first described cases are believed to be of type1 diabetes.[93] Indian physicians around the same time identified the disease and classified it as madhumeha or "honey urine", noting the urine would attract ants.[93] The term "diabetes" or "to pass through" was first used in 230BCE by the Greek Apollonius of Memphis.[93] The disease was considered rare during the time of the Roman empire, with Galen commenting he had only seen two cases during his career.[93] This is possibly due to the diet and lifestyle of the ancients, or because the clinical symptoms were observed during the advanced stage of the disease. Galen named the disease "diarrhea of the urine" (diarrhea urinosa). The earliest surviving work with a detailed reference to diabetes is that of Aretaeus of Cappadocia (2nd or early 3rd century CE). He described the symptoms and the course of the disease, which he attributed to the moisture and coldness, reflecting the beliefs of the "Pneumatic School". He hypothesized a correlation of diabetes with other diseases and he discussed differential diagnosis from the snakebite which also provokes excessive thirst. His work remained unknown in the West until 1552, when the first Latin edition was published in Venice.[94]

Type1 and type2 diabetes were identified as separate conditions for the first time by the Indian physicians Sushruta and Charaka in 400-500CE with type1 associated with youth and type2 with being overweight.[93] The term "mellitus" or "from honey" was added by the Briton John Rolle in the late 1700s to separate the condition from diabetes insipidus, which is also associated with frequent urination.[93] Effective treatment was not developed until the early part of the 20th century, when Canadians Frederick Banting and Charles Herbert Best isolated and purified insulin in 1921 and 1922.[93] This was followed by the development of the long-acting insulin NPH in the 1940s.[93]

The word diabetes ( or ) comes from Latin diabts, which in turn comes from Ancient Greek (diabts) which literally means "a passer through; a siphon."[95]Ancient Greek physician Aretaeus of Cappadocia (fl. 1st century CE) used that word, with the intended meaning "excessive discharge of urine", as the name for the disease.[96][97] Ultimately, the word comes from Greek (diabainein), meaning "to pass through,"[95] which is composed of - (dia-), meaning "through" and (bainein), meaning "to go".[96] The word "diabetes" is first recorded in English, in the form diabete, in a medical text written around 1425.

The word mellitus ( or ) comes from the classical Latin word melltus, meaning "mellite"[98] (i.e. sweetened with honey;[98] honey-sweet[99]). The Latin word comes from mell-, which comes from mel, meaning "honey";[98][99] sweetness;[99] pleasant thing,[99] and the suffix -tus,[98] whose meaning is the same as that of the English suffix "-ite".[100] It was Thomas Willis who in 1675 added "mellitus" to the word "diabetes" as a designation for the disease, when he noticed the urine of a diabetic had a sweet taste (glycosuria). This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, Indians, and Persians.

The 1989 "St. Vincent Declaration"[101][102] was the result of international efforts to improve the care accorded to those with diabetes. Doing so is important not only in terms of quality of life and life expectancy but also economicallyexpenses due to diabetes have been shown to be a major drain on healthand productivity-related resources for healthcare systems and governments.

Several countries established more and less successful national diabetes programmes to improve treatment of the disease.[103]

People with diabetes who have neuropathic symptoms such as numbness or tingling in feet or hands are twice as likely to be unemployed as those without the symptoms.[104]

In 2010, diabetes-related emergency room (ER) visit rates in the United States were higher among people from the lowest income communities (526 per 10,000 population) than from the highest income communities (236 per 10,000 population). Approximately 9.4% of diabetes-related ER visits were for the uninsured.[105]

The term "type1 diabetes" has replaced several former terms, including childhood-onset diabetes, juvenile diabetes, and insulin-dependent diabetes mellitus (IDDM). Likewise, the term "type2 diabetes" has replaced several former terms, including adult-onset diabetes, obesity-related diabetes, and noninsulin-dependent diabetes mellitus (NIDDM). Beyond these two types, there is no agreed-upon standard nomenclature.

Diabetes mellitus is also occasionally known as "sugar diabetes" to differentiate it from diabetes insipidus.[106]

In animals, diabetes is most commonly encountered in dogs and cats. Middle-aged animals are most commonly affected. Female dogs are twice as likely to be affected as males, while according to some sources, male cats are also more prone than females. In both species, all breeds may be affected, but some small dog breeds are particularly likely to develop diabetes, such as Miniature Poodles.[107] The symptoms may relate to fluid loss and polyuria, but the course may also be insidious. Diabetic animals are more prone to infections. The long-term complications recognised in humans are much rarer in animals. The principles of treatment (weight loss, oral antidiabetics, subcutaneous insulin) and management of emergencies (e.g. ketoacidosis) are similar to those in humans.[107]

Inhalable insulin has been developed.[108] The original products were withdrawn due to side effects.[108] Afrezza, under development by pharmaceuticals company MannKind Corporation, was approved by the FDA for general sale in June 2014.[109] An advantage to inhaled insulin is that it may be more convenient and easy to use.[110]

Transdermal insulin in the form of a cream has been developed and trials are being conducted on people with type 2 diabetes.[111][112]

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Diabetes mellitus - Wikipedia

Program Goal:The biotechnology program is designed to prepare students for employment as technicians who will work in a laboratory or industrial setting. Biotechnology is a wide-ranging field encompassing: DNA/RNA and protein isolation, characterization, and sequencing; cell culture; genetic modification of organisms; toxicology; vaccine sterility testing; antibody isolation and production; and the development of diagnostic and therapeutic agents. This hands-on program is designed to meet local, statewide, and national need for laboratory technicians. Graduates are thoroughly grounded in basic laboratory skills and trained in advanced molecular biology techniques. Students are acclimated to both research and industrial environments. The program emphasizes laboratory-based, universal, and scalable technical skills resulting in a thorough and comprehensive understanding of the methodology.

Program Entrance Requirements: To be admitted into the biotechnology Degree Program, a student must have,

Achieved a level of English and reading proficiency which qualifies the student for entry into ENC 1101 or higher as demonstrated by the standard placement criteria currently in use at State College of Florida, Manatee-Sarasota (SCF)

Achieved a level ofmathematics proficiency which qualifies the student for entry into MAC 1105 or higher as demonstrated by the standard placement criteria currently in use at SCF

Achieved a level of chemistry and biological content proficiency equivalent to that covered in CHM 1025C and BSC 1007C as demonstrated by the standard placement criteria currently in use at SCF

Suggested course of study:

1

3

College Algebra

MAC 1105

3

4

Total Hours

12

4

3

Social and

Behavioral

Sciences

Must be an area III

Socialor Behavioral Science.

3

4

Total Hours

13

4

4

3

Total Hours

11

4

4

5

Total Hours

13

3

5

3

4

Total Hours

12

See more here:
Biotechnology A.S. Degree

Track 1:Pharmaceutical Biotechnology

Pharmaceutical Biotechnology is the science that covers all technologies required for producing, manufacturing and registration of biological drugs.Pharmaceutical Biotechnologyis an increasingly important area of science and technology. It contributes in design and delivery of new therapeutic drugs,diagnosticagents for medical tests, and in gene therapy for correcting the medical symptoms of hereditary diseases. The Pharmaceutical Biotechnology is widely spread, ranging from many ethical issues to changes inhealthcarepractices and a significant contribution to the development of national economy.Biopharmaceuticalsconsists of large biological molecules which areproteins. They target the underlying mechanisms and pathways of a disease or ailment; it is a relatively young industry. They can deal with targets in humans that are not accessible with traditional medicines.

RelatedBiotechnology Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrialBiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA; Global Biotechnology Congress 2016, May 11th - 14th 2016, Boston, MA, USA;BiomarkerSummit 2016, March 21-23, 2016 San Diego, CA, USA; 14th Vaccines Research & Development, July 7-8, 2016 Boston, USA; Pharmaceutical &Biotech Patent LitigationForum, Mar 14 - 15, 2016, Amsterdam, Netherlands;

Track 2:Biotechnology in Health Care

Biotechnology in health care represents the complex of modern biological approaches in the field of healthcare research and industry. Healthcare Biotechnology methods are used primarily in pharmaceutical industry and modern clinical diagnostics. The research training in this domain is programmed for the candidates intending to develop their careers in scientific-research institutions, clinical anddiagnostic laboratories, analytical services,pharmacologicalandpharmaceutical companies, etc. For the first time in the history of human healthcare, biotechnology is enabling the development and manufacturing of therapies for a number of rare diseases with a genetic origin. Although individually rare, collectively thesediseasesaffect some 20-30 million individuals and their families with 70-80% having a genetic component requiring biotechnology as part of the solution.

RelatedBiotechnology Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrialBiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA; 3rd CaribbeanBiomedicalResearch Days, January 16-18, 2016, Rodney Bay, Saint Lucia; GlobalBiotechnologyCongress 2016, May 11th-14th 2016, Boston, MA, USA;BiomarkerSummit 2016, March 21-23, 2016 San Diego, CA, USA; 14thVaccinesResearch & Development, July 7-8, Boston, USA;Pharmaceutical&BiotechPatentLitigation Forum, Mar 14 - 15, 2016, Amsterdam, Netherlands; 4thBiomarkersinDiagnostics, Oct 07-08, 2015 Berlin, Germany, DEU.

Track 3:Food Biotechnology

Food biotechnology is a process scientists use to enhance the production,nutritional value, safety, and taste of foods. It can also benefit the environment by improving crops so that they need fewerpesticides. The concept is not new: For centuries farmers have selectively bred plants to pass on desirable qualities. For example, our ancestors began by replanting only corn seeds from the highest yielding and best tasting corn they grew each year. This process selected desirable genes and fixed them by growing the seeds of the selected crop year after year. The result: the golden, deliciously sweet product we now enjoy. Modernfood biotechnologyis a refined version of this same process. Today, scientists obtain desired traits by adding or removing plant genes. This process is called genetic engineering or recombinant DNA technology. It yields foods that are flavorful, contain more vitamins and minerals, and absorb less fat when cooked, and gives us crops that are more resistant to pests and insects. Food biotechnology holds great promise for the future. Soon, fruits and vegetables may be made to resist drought. We may remove allergens from foods such as nuts. Scientists may develop plants that absorb nitrogen more efficiently and need lessfertilizer. The benefits are nearly limitless!

RelatedBiotechnology Conferences

3rdGlobal Food Safety Conference, September 01-03, 2016, Atlanta USA; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrialBiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA;BiologicallyActive Compounds inFood, October 15-16 2015 Lodz, Poland; World Conference on InnovativeAnimal NutritionandFeeding, October 15-17, 2015 Budapest, Hungary; 18th International Conference onFood ScienceandBiotechnology, November 28 - 29, 2016, Istanbul, Turkey; 18th International Conference onAgricultural Science,Biotechnology,FoodandAnimal Science, January 7 - 8, 2016, Singapore; International IndonesiaSeafood and Meat, 1517 October 2016, Jakarta, Indonesia; International Conference of Eco-friendlyApplied BiologicalControl ofAgricultural PestsandPhytopathogens, 19 -22 October 2015, Cairo, Egypt;Food Structures,DigestionandHealth3rd International Conference, 28-30 October, Wellington, New Zealand; Conference ofCereal BiotechnologyandBreeding, November 2-4, 2015, Berlin, Germany; AdvancedWater TreatmentforFood & Beverage, November 3-4, 2015 Amsterdam, Netherlands.

Track 4:Industrial and Microbial Biotechnology

Industrial or white biotechnology uses enzymes and micro-organisms to make biobased products in sectors such as chemicals,food and feed, detergents, paper and pulp, textiles andbioenergy. The application of industrial biotechnology has been proven to make significant contributions towards mitigating the impacts of climate change in these and other sectors. In addition to environmental benefits, biotechnology can improve industrys performance and product value and, as the technology develops and matures,white biotechnologywill yield more and more viable solutions for our environment. These innovative solutions bring added benefits for both our climate and our economy.

RelatedBiotechnology Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrialBiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA; BIO IPCC Conference, Cary, North Carolina, USA; World Congress onIndustrial Biotechnology, April 17-20, 2016, San Diego, CA; The European Forum forIndustrial Biotechnologyand theBioeconomy, 27-29 October 2015, Brussels, Belgium; 4thBiotechnologyWorld Congress, February 15th-18th, 2016, Dubai, United Arab Emirates; International Conference on Advances inBioprocess EngineeringandTechnology, 20th to 22nd January 2016,Kolkata, India; GlobalBiotechnologyCongress 2016, May 11th - 14th 2016, Boston, MA, USA

Track 5:Nanobiotechnology

Nanobiotechnologyis beginning to allow scientists, engineers, and physicians to work at the cellular and molecular levels to produce major benefits to life sciences and healthcare. In the next century, the emerging field of nanotechnology will lead to new biotechnology based industries and novel approaches in medicine. Nanobiotechnology is that branch of nanotechnology that deals with biological and biochemical applications or uses. Nanobiotechnology often studies existing elements of living organisms and nature to fabricate newnano-devices. Generally, nanobiotechnology refers to the use of nanotechnology to further the goals of biotechnology. Some of the innovative challenges in the field of biology are: New molecular imaging techniques, Quantitative analytical tools, Physical model of the cell as a machine, Better ex-vivo tests and improvement in current laboratory techniques and Better drug delivery systems.

RelatedBiotechnology Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrial BiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA;NanoBioTech-Montreux, November 16-18, 2015, Switzerland; International Conference onNanobiotechnology(ICNB'16), April 1-2, 2016, Prague, Czech Republic; InternationalNanotechnologyConference & Expo, April 4-6, 2016 Baltimore, USA;

Track 6:Plant Biotechnology

Plant biotechnology is the technique used to manipulate the plants for specific needs or requirement. In traditional process seed is the major source for germinating a new plant but the advance method is independent that combines multiple needs to get the required traits.Plant biotechnologymeets the challenge that includesgenomics,genetic engineering,tissue culture, andtransgenic cropsetc. These biotechnological applications allow researchers to detect and map genes and discover their functions, selection of specific genes in genetic resources and its breeding and to customize the plant according to the requirement by transferring the genes of specific traits to combine with others to create a new species. The recent advances in plant biotechnology provide potential way to make improvements much more quickly than conventionalplant breedingtechniques. Plant tissue culture is a part of plant biotechnology which is the collection of many techniques that is used to maintain and grow plant, plant cells, plant tissues under controlled sterile conditions over the nutrient medium. Plant tissue culture is the convenient method produce clones of a plant through the process calledmicropropagation. The main advantage of this method is to produce exact and multiple copies of plants with good desired properties like good flowers, fruits and other characters within small span of time. Production of multiple plants without seed, production of genetically modified plants, the tissue culture plants are resistant to the diseases,pathogensand pests, also it is the best method to store the gene pools and many more

RelatedBiotechnology Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrialBiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA; 3rd CaribbeanBiomedicalResearch Days, January 16-18, 2016, Rodney Bay, Saint Lucia;Global BiotechnologyCongress 2016, May 11th - 14th 2016, Boston, MA, USA; 18th International Conference onAgricultural Biotechnology, Biological and Biosystems Engineering, January 18-19, 2016, London, United Kingdom; 2nd International Conference on Biotechnology andAgriculture EngineeringApril 08-09 2016 in Tokyo, Japan; Food Structures, Digestion andHealth3rd International Conference, 28-30 October 2015, Wellington, New Zealand; 3rd Conference ofCereal Biotechnologyand Breeding, November 2-4, 2015, Berlin, Germany;

Track 7:Agricultural Biotechnology

Agricultural biotechnologyis the area of biotechnology involving applications to agriculture. Agricultural biotechnology has been practiced for a long time, as people have sought to improve agriculturally important organisms by selection and breeding. An example of traditional agricultural biotechnology is the development of disease-resistant wheat varieties by cross-breeding different wheat types until the desired disease resistance was present in a resulting new variety. Modern agricultural biotechnology improves crops in more targeted ways. The best known technique is genetic modification, but the term agricultural biotechnology (or green biotechnology) also covers such techniques as Marker Assisted Breeding, which increases the effectiveness of conventional breeding. Whatever the particular technology used, the crops may be destined for use for food,biomaterialsor energy production.Genetic modificationmeans that existing genes are modified or new genes included to give plant varieties desirable characteristics, such as resistance to certain pests or herbicides, or forvitaminfortification. Because only a few genes with known traits are transferred, GM methods are more targeted and faster thantraditional breeding. Biotechnology has helped to increase crop productivity by introducing such qualities as disease resistance and increased drought tolerance to the crops.

RelatedBiotechnology Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrialBiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA; Conference onAgricultural Statistics2015, Sarawak, Malaysia; 2nd International Conference onGlobal Food Security, 11-14 October 2015, Ithaca, United States; 5th International Conference onOrganic AgricultureSciences, 14th-17th October 2015, Bratislava, Slovakia; 18thInternational Conference onAgricultural, Biotechnology, Biological and Biosystems Engineering, January 18-19, 2016, London, United Kingdom; 2nd International Conference on Biotechnology andAgriculture EngineeringApril 08-09 2016 in Tokyo, Japan;Food Structures, Digestion andHealth3rd International Conference, 28-30 October 2015, Wellington, New Zealand; 3rd Conference of Cereal Biotechnology andBreeding, November 2-4, 2015, Berlin, Germany; AdvancedWater TreatmentforFood & Beverage, 3-4 Nov 2015, Amsterdam, Netherlands

Track 8:Environmental Biotechnology

Environmental biotechnology is biotechnology that is applied to and used to study the natural environment. Environmental biotechnology could also imply that one try to harness biological process for commercial uses and exploitation. The International Society for Environmental Biotechnology defines environmental biotechnology as "the development, use and regulation of biological systems for remediation of contaminated environments (land, air, water), and for environment-friendly processes (green manufacturing technologies and sustainable development)

RelatedBiotechnology Conferences

5th International Conference onBiodiversity, March 10-12, 2016 at Madrid, Spain; International Conference on Biotechnology andEnvironmental ManagementSeptember 14-15 Milan, Italy; 6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrial BiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA; International Conference onGreen Energy& Expo September 21-23, 2015 Orlando, FL, USA; International Conference on Environment,Energy and Biotechnology, May 25, 2016 Jeju Island, Republic of Korea; International Conference on Energy andEnvironmental Biotechnology, November 24 - 25, 2015 Dubai, UAE; Science for theEnvironmentConference 2015, October 1-2 2016 Aarhus, Denmark; International Conference onEnvironmental Scienceand Technology 14th to 17th May 2016, Antalya, Turkey

Track 9:Marine Biotechnology

Marine Biotechnology is a relatively new field of study, having emerged in the past few years. The Marine Biotechnology is intended to host scientific contributions inmarine sciencethat are based on the enormousbiodiversityof marine ecosystems and the genetic uniqueness of marine organisms to develop useful products and applications.Aquaculture& Marine Biotechnology have been the subject of great importance not only because of the sustainable utilization of their resources to feed the billion people of the world but also for the future challenges for discovery of new products and process development of economic importance through its treasure recognition and diversification. Apart from contributing to high quality and healthy food (aquaculture),nutraceuticalsand medicinal products (anti-cancer andantimicrobials), this sector is expected to contribute to sustainable alternative source of energy (biofuelfrom microalgae) and environmental health. Marine Biotechnology is capable of making an important contribution towards meeting impending challenges like a sustainable supply of food and energy and human health.

RelatedBiotechnology Conferences

5th International Conference on Biodiversity, March 10-12, 2016 at Madrid, Spain; International Conference on Biotechnology and Environmental Management September 14-15, Milan, Italy; 6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrial BiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA;BioMarine2015, 12-14 Oct 2016, Wilmington, NC, United States; International Conference onMarine BiotechnologyandBioprocessing, December 10 - 11, 2015, Sydney, Australia; Annual world congress ofMarine Biotechnology-2015, November 6-8 2015, Qingdao, China;Global BiotechnologyCongress 2016, May 11th - 14th 2016, Boston, MA, USA; Annual InternationalMarine BiotechnologyConference, Nov 20, 2013, Brisbane, Australia

Track 10:Current Scenario of Biotechnology

Due to multidisciplinary nature of the field of biotechnology, a wide range of different branches of science have made significant contributions to the fast development of this field. Some of these disciplines are-biochemical engineering,physiology,biochemistry,food science,material science,bioinformatics,immunology,molecular biology,chemical engineeringetc. Biotechnology is also improving the lives of people around the world. Biotechnology also has affected economy in a positive way due to the creation and growth of small business, generation of new jobs. Agricultural biotechnology has reduced our dependency on pesticides.Bioremediation technologiesare being used to clean our environment by removing toxic substances from contaminated ground water and soils. about 60% of the biotechnology products in the market are healthcare products and 21% are products used in agriculture andanimal husbandry. A considerable amount of efforts in research are on, to use and extract benefit from this interesting and upcoming field for the betterment of human life and the environment. Many biochemical companies are involved in the production of biotechnological products usinggenetic engineeringtechniques.

RelatedBiotechnology Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrial BiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA;Global BiotechnologyCongress 2016, May 11th - 14th 2016, Boston, MA, USA;Global BiotechnologyCongress 2016, May 11th - 14th 2016, Boston, MA, USA;

Track 11:Animal Biotechnology

Biotechnology provides new tools for improvinghuman healthand animal health and welfare and increasinglivestock productivity. Biotechnology improves the food we eat-meat, milk and eggs. Biotechnology can improve an animals impact on the environment. And biotechnology enhances ability to detect, treat and prevent diseases. Just like other assistedreproduction techniquessuch asartificial insemination,embryo transferandin vitro fertilization, livestockcloningimproves animal breeding programs allowing farmers and ranchers to produce healthier offspring, and therefore producer healthier, safer and higher quality foods more consistently.

RelatedBiotechnology Conferences|Biotechnology Events|Biochemistry Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrial BiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA;Global BiotechnologyCongress 2016, May 11th - 14th 2016, Boston, MA, USA;BiomarkerSummit 2016, March 21-23, 2016 San Diego, CA, USA; 14thVaccinesResearch & Development, July 7-8, Boston, USA;

Track 12:Biomass and Bioenergy

Bioenergyis the chemical energy contained in organic matter (biomass) which can be converted into energy forms that we can use directly, such as electricity, heat and liquid fuel. Biomass is any organic matter of recently living plant or animal origin. Unlike coal, the organic matter is notfossilised.Bioenergy plantscan range from small domestic heating systems to multi-megawatt industrial plants requiring hundreds of thousands of tonnes ofbiomassfuel each year. A variety of technologies exists to release and use the energy contained in biomass. They range from combustion technologies that are well proven and widely used around the world for generating electricity generation, to emerging technologies that convert biomass intoliquid fuelsfor road, sea and air transport.

RelatedBiotechnology Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrial BiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA;Global BiotechnologyCongress 2016, May 11th - 14th 2016, Boston, MA, USA; IEABioenergyConference 2016, October 26th-29th2016, Berlin, Germany; Summit onIndustrial biotechnologyandBioenergy, December 7 -9, 2016 San Diego, California; Energy Conference, Des Moines, Oct 13-15 Iowa, USA; EuropeanBiomassConference and Exhibition Amsterdam, 6-9, June, Germany Netherlands; EcoSummit 2016, August 29 - September 01 2016, Montpellier, France; InternationalBioenergyand Bioproducts Conference, October 28-30, 2016 Atlanta, Georgia; 2016 InternationalBiomassConference & Expo, Charlotte, North Carolina;World Bioenergy2016, May 24-26 2016, Stockholm, Sweden; 2016 InternationalFuel EthanolWorkshop & Expo, June 20-23, 2016 Milwaukee, Wisconsin.

Track 13:Biotechnology and its Applications

The applications of biotechnology are so broad, and the advantages so compelling, that virtually every industry is using this technology. Developments are underway in areas as diverse aspharmaceuticals, diagnostics,textiles,aquaculture,forestry, chemicals, household products,environmental cleanup,food processingand forensics to name a few. Biotechnology is enabling these industries to make new or better products, often with greater speed, efficiency and flexibility. Biotechnology holds significant promise to the future but certain amount of risk is associated with any area.

RelatedBiotechnology Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrial BiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA;Global BiotechnologyCongress 2016, May 11th - 14th 2016, Boston, MA, USA; IEABioenergyConference 2016, October 26th-29th2016, Berlin, Germany; Summit onIndustrial biotechnologyandBioenergy, December 7 -9, 2016 San Diego, California;Global BiotechnologyCongress 2016, May 11th - 14th 2016, Boston, MA, USA;

Track 14:Biotechnology Market

The growth of Biotechnology industry as per Transparency Market Research is estimated to observe substantial growth during 2010 and 2017 as investments from around the world are anticipated to rise, especially from emerging economical regions of the world. The report states that the global market for biotechnology, studied according to its application areas, shall grow at an average annual growth rate of CAGR 11.6% from 2012 to 2017 and reach a value worth USD 414.5 billion by the end of 2017. This market was valued approximately USD 216.5 billion in 2011. The market of bioagriculture, combined with that of bioseeds, is projected to reach a value worthUSD 27.46 billionby 2018. The field of biopharmaceuticals dominated the global biotechnology market and accounted for 60% shares of it in the year 2011. Many biotechnological industries flourished by the technological advancements leading to new discoveries and rising demands from the pharmaceutical and agricultural sectors.

RelatedBiotechnology Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrial BiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA;Global BiotechnologyCongress 2016, May 11th - 14th 2016, Boston, MA, USA;BIO Investor Forum, October 20-21, 2015, San Francisco, USA; BIO Latin America Conference, October 14-16, 2015, Rio de Janeiro, Brazil; BioPharm Americ 2015-8thAnnual International Partnering Conference, September 15-17, 2015, Boston, MA, USA;

Track 15: Biotech Companies and Market Analysis

The biotechnology community in Europe has seen significant growth in recent years. By establishing itself in several key niche markets, the European biotech and pharma industries have thrived in the global biopharmaceutical market. Europe high standards for their life science educational systems have increased the level of growth and the quality of Europes workforce and broadened Europes reach within the world. With a dedication to innovation and research, Europe has established itself as a leader in biotechnology.

RelatedBiotechnology Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrial BiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA;Global BiotechnologyCongress 2016, May 11th - 14th 2016, Boston, MA, USA;BIO Investor Forum, October 20-21, 2015, San Francisco, USA; BIO Latin America Conference, October 14-16, 2015, Rio de Janeiro, Brazil; BioPharm Americ 2015-8thAnnual International Partnering Conference, September 15-17, 2015, Boston, MA, USA;

Track 16: Biotech Startups and Funding:

Biotechnology being an emerging industry, game-changing strategies and relevant application of the knowledge-intelligence resource pool, drive the process of growth. Europe Biotechnology seeks to enhance, enrich and encourage newer innovations, path-breaking discoveries and effective solutions in the industry by offering a vibrant global platform for convergence of the key stakeholders - Biotech & Biopharma Companies, research institutions, investors, service providers, policy makers, regulators and analysts.

RelatedBiotechnology Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrial BiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA;Global BiotechnologyCongress 2016, May 11th - 14th 2016, Boston, MA, USA;BIO Investor Forum, October 20-21, 2015, San Francisco, USA; BIO Latin America Conference, October 14-16, 2015, Rio de Janeiro, Brazil; BioPharm Americ 2015-8thAnnual International Partnering Conference, September 15-17, 2015, Boston, MA, USA;

Track 17: Advances in Biotech Manufacturing

The biotechnology community in Asia has seen significant growth in recent years. By establishing itself in several key niche markets, the European biotech and pharma industries have thrived in the global biopharmaceutical market. Asias high standards for their life science educational systems have increased the level of growth and the quality of Asias workforce and broadened Asias reach within the world. With a dedication to innovation and research, Asia has established itself as a leader in biotechnology.

RelatedBiotechnology Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrial BiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA;Global BiotechnologyCongress 2016, May 11th - 14th 2016, Boston, MA, USA;BIO Investor Forum, October 20-21, 2015, San Francisco, USA; BIO Latin America Conference, October 14-16, 2015, Rio de Janeiro, Brazil; BioPharm Americ 2015-8thAnnual International Partnering Conference, September 15-17, 2015, Boston, MA, USA;

Track 18: Biotech Investors and Grants

The biotechnology industry hauled in $2.3 billion worth of venture capital investments during the second quarter of this yeara 32% increase over the prior quarter, according to the newest MoneyTree Report from PricewaterhouseCoopers (PwC) and the National Venture Capital Association (NVCA), with data from Thomson Reuters. The 126 deals struck during the period marked the biggest quarterly investment in biotech since the MoneyTree report first came out in 1995, and it brought the total for the first half to $3.8 billion.

RelatedBiotechnology Conferences

6thWorld Congress onBiotechnology, October 05-07, 2016, New Delhi India; 10thAsia PacificBiotechCongress July 25-27, 2016, Bangkok, Thailand; 2ndIndustrial BiotechnologyCongress, July 28-29, 2016, Berlin, Germany; 12thBiotechnologyCongress, Nov 14-15, 2016, San Francisco, USA;Global BiotechnologyCongress 2016, May 11th - 14th 2016, Boston, MA, USA;BIO Investor Forum, October 20-21, 2015, San Francisco, USA; BIO Latin America Conference, October 14-16, 2015, Rio de Janeiro, Brazil; BioPharm Americ 2015-8thAnnual International Partnering Conference, September 15-17, 2015, Boston, MA, USA;

8th Euro Biotechnology Congress (Euro Biotechnology-2015) was held during August 18-20, 2015 at Flemings Conference Hotel, Frankfurt, Germany. The conference was marked with the attendance of Editorial Board Members of supported OMICS Group Journals, Scientists, young and brilliant researchers, business delegates and talented student communities representing more than 30 countries, who made this conference fruitful and productive.

This conference was based on the theme Biotechnology for a Better Tomorrow which included the following scientific tracks:

Biotechnology in Health Care Environmental Biotechnology Industrial Aspects of Biotechnology Stem Cells and Regenerative Medicine Marine Biotechnology and Aquaculture Agriculture Biotechnology Animal Biotechnology Food and Bio Process Biotechnology Cell and Molecular Biology Nanobiotechnology Genetic Engineering and rDNA Technology Current Scenarios and other allied areas of Biotechnology

We are thankful to our below Honourable guests and Keynote Speakers for their generous support and suggestions.

Manfred T Reetz Philipps-University, Germany

W Tim Miller - Echelon-Frontier Scientific Inc, USA

Wilfried Schwab - Technische Universitt Mnchen, Germany

Aline Zimmer- Merck Millipore, Germany

The conference proceedings were carried out through various Scientific-sessions and plenary lectures, of which the following topics were highlighted as Keynote-presentations:

Increasing the efficiency of directed evolution of enzymes: Manfred T Reetz, Philipps-University of Marburg, Germany

Trade secrets and laboratory security: Frontier Scientific Inc, USA

Aroma glucoside production: Wilfried Schwab, Technische Universitt Mnchen, Germany

Chemically modified cysteine in fed-batch processes and impact on CHO specific productivity: Aline Zimmer, Merck Millipore, USA

Synthetic mRNAs present a rapidly growing technology: Optimized tool for stem cell generation and for manipulating cellular phenotypes : Guido Krupp, Amptec GmbH, Germany

Novel synthetic anti-microbial defensins through confrontational selection and screening of yeast libraries: K Yankulov, University of Guelph, Canada

Long acting recombinant glycoprotein hormones: From bench to clinics, Fuad Fares, University of Haifa, Israel

Poster Session was judged by K Yankulov, University of Guelph, Canada

The esteemed guests, Keynote speakers, well-known researchers and delegates shared their innovative research and vast experience through their fabulous presentations at the podium of grand Euro Biotechnology-2015. We are glad to inform that all accepted abstracts for the conference have been published in OMICS Group Journal of Biotechnology & Biomaterials as a special issue.

We are also obliged to various delegate experts, company representatives and other eminent personalities who supported the conference by facilitating active discussion forums. We sincerely thank the Organizing Committee Members for their gracious presence, support, and assistance. With the unique feedback from the conference, OMICS Group would like to announce the commencement of the 11th Euro Biotechnology Congress" to be held during November 07-09, 2016 at Alicante, Spain

Let us meet Again @ Euro Biotechnology-2016

Biotechnology-2014

OMICS Group Conferencessuccessfully hosted its premier5thWorld Congress on Biotechnologyduring June25-27, 2014 Valencia Conference centre, Valencia Spain

This World congress was accomplished by the support of European Biotechnology Thematic Network Association (EBTNA), Valencia Bioregion (BIOVAL), Federation of Spanish Biotechnologist (FEBiotec) and Societ Italo-Latinoamericana di Etnomedicina (SILAE). Biotechnology-2014 marked with the attendance of Editorial Board Members of supported OMICS Group Journals, Scientists, young and brilliant researchers, business delegates and talented student communities representing more than 25 countries, who made this conference fruitful and productive.

This5thWorld Congress on Biotechnologywas based on the theme the theme Biotechnology: Meeting the Needs of a Changing World which has covered the below scientific sessions:

The conference was greeted by the welcome message ofProf. Cheorl-Ho KimSung Kyun Kwan University, Korea and moderated byProf. Martin J. DSouza, Mercer University, USA. The support was extended by the below honourable guest Em. Prof.Marc Van Montagu, (World Food Laureate 2013) University of Gent, Belgium, Prof.Roberto Gaxiola, Arizona State University, USA, Prof.Ara Kanekanian, Cardiff Metropolitan University, UK, Prof.Manuel P. Alonso,University of Valencia, Spain, Prof.Cheorl-H. Kim,Sung Kyun Kwan University,Dr. Srinubabu Gedela, OMICS Group Inc, USA and below keynote lectures:

OMICS GroupInternational acknowledge the support of below Chairs and Co-chairs foe whom we were able to run smoothly the scientific sessions includes: Alain Goossens, Ghent University, Belgium, Oscar Vicente, IBMCP, Polytechnic University of Valencia, Spain, Ara Kanekanian, Cardiff Metropolitan University, UK, Ana M. Hortigela, Instituto de Medicina Genmica, Spain, Cheorl-H Kim, Sung Kyun Kwan University, Korea, Martin J. DSouza, Mercer University, USA, Marina V. Frontasyeva, Joint Institute for Nuclear Research, Russian Federation, Zlatka Alexieva, Bulgarian Academy of Sciences, Bulgaria, Salvador Ventura, Universitat Autnoma de Barcelona, Spain, Giuseppe Manco, Institute of Protein Biochemistry, National Research Council (CNR), Italy, Aihua Liu, Qingdao Institute of Bioenergy & Bioprocess, CAS, China, Amparo Pascual-Ahuir Giner, Universidad Politecnica de Valencia, Spain.

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Biotechnology Conferences | Biotechnology Events - Europe

UMBC Biotechnology Graduate Programs

The Masters in Professional Studies in Biotechnology prepares science professionals to fill management and leadership roles in biotechnology-related companies or agencies.

UMBCs Biotechnology curriculum is intended to address changes in the needs of the biotechology industry through experiential learning, by providing advanced instruction in the life sciences, in addition to coursework in regulatory affairs, leadership, management, and financial management in a life science-oriented business.

Global challenges in human health, food security, sustainable industrial production and environmental protection continues to fuel the biosciences industry, creating new opportunities within the four primary sub sectors:

UMBC's Biotechnology Graduate Program and its strong academic programs in the life sciences are led by a distinguished faculty of nearly fifty members spanning the departments of:

This established academic and research expertise in the biosciences provides a foundation for programs in biotechnology management and biochemical regulatory engineering.

Over the past decade the industry has added nearly 111,000 new, high-paying jobs or 7.4 percent to its employment base, according to the latest Battelle/BIO report.

Economic output of the bioscience industry has expanded significantly with 17 percent growth for the biosciences since 2007, nearly twice the national private sector nominal output growth.

UMBC Division of Professional Studies 1000 Hilltop Circle, Sherman Hall East 4th Floor, Baltimore, MD 21250 410-455-2336 dps@umbc.edu

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Biotechnology at UMBC

Broadly speaking, biotechnology is any technique that uses living organisms or substances from these organisms to make or modify a product for a practical purpose (Box 2). Biotechnology can be applied to all classes of organism - from viruses and bacteria to plants and animals - and it is becoming a major feature of modern medicine, agriculture and industry. Modern agricultural biotechnology includes a range of tools that scientists employ to understand and manipulate the genetic make-up of organisms for use in the production or processing of agricultural products.

Some applications of biotechnology, such as fermentation and brewing, have been used for millennia. Other applications are newer but also well established. For example, micro-organisms have been used for decades as living factories for the production of life-saving antibiotics including penicillin, from the fungus Penicillium, and streptomycin from the bacterium Streptomyces. Modern detergents rely on enzymes produced via biotechnology, hard cheese production largely relies on rennet produced by biotech yeast and human insulin for diabetics is now produced using biotechnology.

Biotechnology is being used to address problems in all areas of agricultural production and processing. This includes plant breeding to raise and stabilize yields; to improve resistance to pests, diseases and abiotic stresses such as drought and cold; and to enhance the nutritional content of foods. Biotechnology is being used to develop low-cost disease-free planting materials for crops such as cassava, banana and potato and is creating new tools for the diagnosis and treatment of plant and animal diseases and for the measurement and conservation of genetic resources. Biotechnology is being used to speed up breeding programmes for plants, livestock and fish and to extend the range of traits that can be addressed. Animal feeds and feeding practices are being changed by biotechnology to improve animal nutrition and to reduce environmental waste. Biotechnology is used in disease diagnostics and for the production of vaccines against animal diseases.

Clearly, biotechnology is more than genetic engineering. Indeed, some of the least controversial aspects of agricultural biotechnology are potentially the most powerful and the most beneficial for the poor. Genomics, for example, is revolutionizing our understanding of the ways genes, cells, organisms and ecosystems function and is opening new horizons for marker-assisted breeding and genetic resource management. At the same time, genetic engineering is a very powerful tool whose role should be carefully evaluated. It is important to understand how biotechnology - particularly genetic engineering - complements and extends other approaches if sensible decisions are to be made about its use.

This chapter provides a brief description of current and emerging uses of biotechnology in crops, livestock, fisheries and forestry with a view to understanding the technologies themselves and the ways they complement and extend other approaches. It should be emphasized that the tools of biotechnology are just that: tools, not ends in themselves. As with any tool, they must be assessed within the context in which they are being used.

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1. What is agricultural biotechnology? - GreenFacts

What are some average salaries for jobs in the Biotechnology industry? These pages lists all of the job titles in the Biotechnology industry for which we have salary information. If you know the pay grade of the job you are searching for you can narrow down this list to only view Biotechnology industry jobs that pay less than $30K, $30K-$50K, $50K-$80K, $80K-$100K, or more than $100K. If you are unsure how much your Biotechnology industry job pays you can choose to either browse all Biotechnology industry salaries below or you can search all salaries.

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Industry: Aerospace & Defense Biotechnology Business Services Chemicals Construction Edu., Gov't. & Nonprofit Energy & Utilities Financial Services Healthcare Hospitality & Leisure Insurance Internet Media MFG Durable MFG Nondurable Pharmaceuticals Retail & Wholesale Software & Networking Telecom Transportation

Income Level: All $100,000+ $80,000 - $100,000 $50,000 - $80,000 $30,000 - $50,000 $10,000 - $30,000

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Biotechnology Industry Salaries, Bonuses and Benefits ...

The inferior physician treats gross disease

The mediocre physician treats disease just manifesting

The superior physician treats before there is a disease

-- (Yellow Emperor's Inner Canon)

Our Mission

The Center for Primary Care and Integrative Medicine is a primary care clinic thatapplies both eastern and western medicalmodalitiesand provides themost effectivepatient care. Our practice is founded on a few underlying principles/desires:

First, we strongly believe in the value of preventative care, a conceptgrounded intraditional Chinese medicine.Brian Carter's Pulse of Oriental Medicinestates the traditional Chinesedoctor's job was to keep the village from getting sick and they in return would make sure his needs were met. Once theybecame sick, they were unable to take care of the doctor, therefore, it onlymadesense for him to keep them well.Our role is to keep you well before any signs of diseasesurface. By keepingmind, body and spirit inbalance, maintaining appropriate nutrient levels and exercising a positive lifestyle, oneis proactively taking care of themselves.

Second, we believe in natural healing. The body has an innate ability to heal itself, we simply assist you on your journey towards wellness. While western medication is effective at treating many illnesses, it can also act as a double-edged sword; the chemicals in pills and other drugs can have many potentiallyharmful side effects. Ourdoctors takea comprehensive look at your medicalconcerns and prescribe the healthiest solution that isindividualized for your needs.

Third, the Center for Primary Care and Integrative Medicine seeks to reduce the increasingly prevalent abuse of narcotics. The United States consumes 60% of the world's narcotics, and these are increasingly prescribed unnecessarily. This has adverse effects on the patient's body. This is not to say that medication/narcotics are bad, but we should reduce their use as much as possible without compromising pain control. Today, more and more people are turning tonatural methods of healing. The Center for Primary Care and Integrative Medicineincorporates the best of conventional and alternative medicine to provide the highest quality of carepossible.

While preventing chronic disease has been our main focus of practice, we emphasize the importance of helping patients who already suffer from a variety of chronic diseases actively recover. In addition to regular cardiopulmonary rehab, we offer Taichi, massage, and acupuncture to help patients from a variety of chronic conditions, e.g., chronic Congestive Heart Failure, COPD, Parkinsons disease, etc., improve functional status. Studies have shown that acupuncture and Taichi can favorably affect heart rate variability and thus decrease post-myocardial infarct mortality. Taichi-based cardiac rehabilitation was associated with an increase in peak oxygen consumption, a marker of functional capacity, in patients with recent MI. Acupuncture has been shown to reduce interleukin-17 (IL-17, inflammation marker) in asthmatic patients and increase 6 minute walking distance and quality of life in COPD patients. Taichi and Scalp acupuncture effectively slow down disease progress in Parkinsons disease patients and improve quality of life.

Last, but not least, we strive to reduce the cost of medicine for both individuals and the nation. Health care costs have been rising for several years and remains a focus of worldwide discussion. National health expenditures have doubled over the past decade from $1.3 trillion in 2000 to $2.6 trillion in 2010. Total health care expenditures grew at an annual rate of 4.4 percent in 2008,outpacing inflation and the growth in national income. Indeed, we are a nation providing the best "sick" care. If we looked atreplacing"sick" care with preventative medicine,wewould be a healthierand wealthier nation. Spending on new medical technology and prescription drugs has been cited as a leading contributor to the increase in overall health. The Center for Primary Careand Integrative Medicine focuses on prevention and treatmentof chronic diseases such as hypertension, diabetes, obesity, and chronic pain.Integrative medicinehas been known to be highly effective in the treatment of such illnesses. In addition,the Center also gives consults to patients who want to learn taichi and yoga to improve well being.

Center for primary care and Integrative Medicine has also been actively collaborating with world renowned institutes to explore mechanisms underlying the effects of acupuncture, Ethnopharmacology, and the application of traditional Chinese Medicine in health regimen.

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Houston Integrative Medicine - Home - Houston, TX

What is Stem Cell Therapy? Stem Cell Therapy (SCT), provides the body with stem cells in the location where it is most needed in order to assist in the healing and regeneration of its existing cells. Contact us to find a doctor/clinic near you who can provide you with therapy using Stemaid Embryonic Stem-Cells. About Us Stemaid provides Embryonic Stem Cells and unique protocols to doctors in order to help their patients who face major health conditions as well as individuals who simply wish to stay young and healthy. Over the past five years of development, we have successfully conducted research into targeted major diseases related to lung, kidney, liver and heart failures, we have aided in helping people who have suffered stroke or brain injury to walk or talk again, we have removed all traces of tumor in multiple cancer patients and we have achieved significant results in fighting aging and its physical markers. You may see a more detailed and referenced list of these successes here.

Embryonic Stem cell treatments have not been approved by FDA. For this reason, we are located abroad. If you are interested in our technology or would like us to put you in touch with the nearest clinic to you who can provide you with stem-cells, please contact us here .

Call us toll-free on 1-844-STEMAID

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Stemaid : Embryonic Stem-cells

Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide (through mitosis) to produce more stem cells. They are found in multicellular organisms. In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cellsectoderm, endoderm and mesoderm (see induced pluripotent stem cells)but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues.

There are three known accessible sources of autologous adult stem cells in humans:

Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank his or her own blood for elective surgical procedures.

Adult stem cells are frequently used in various medical therapies (e.g., bone marrow transplantation). Stem cells can now be artificially grown and transformed (differentiated) into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves. Embryonic cell lines and autologous embryonic stem cells generated through somatic cell nuclear transfer or dedifferentiation have also been proposed as promising candidates for future therapies.[1] Research into stem cells grew out of findings by Ernest A. McCulloch and James E. Till at the University of Toronto in the 1960s.[2][3]

The classical definition of a stem cell requires that it possess two properties:

Two mechanisms exist to ensure that a stem cell population is maintained:

Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.[4]

In practice, stem cells are identified by whether they can regenerate tissue. For example, the defining test for bone marrow or hematopoietic stem cells (HSCs) is the ability to transplant the cells and save an individual without HSCs. This demonstrates that the cells can produce new blood cells over a long term. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.

Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, in which single cells are assessed for their ability to differentiate and self-renew.[7][8] Stem cells can also be isolated by their possession of a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells shall behave in a similar manner in vivo. There is considerable debate as to whether some proposed adult cell populations are truly stem cells.[citation needed]

Embryonic stem (ES) cells are the cells of the inner cell mass of a blastocyst, an early-stage embryo.[9] Human embryos reach the blastocyst stage 45 days post fertilization, at which time they consist of 50150 cells. ES cells are pluripotent and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta.

During embryonic development these inner cell mass cells continuously divide and become more specialized. For example, a portion of the ectoderm in the dorsal part of the embryo specializes as 'neurectoderm', which will become the future central nervous system.[10] Later in development, neurulation causes the neurectoderm to form the neural tube. At the neural tube stage, the anterior portion undergoes encephalization to generate or 'pattern' the basic form of the brain. At this stage of development, the principal cell type of the CNS is considered a neural stem cell. These neural stem cells are pluripotent, as they can generate a large diversity of many different neuron types, each with unique gene expression, morphological, and functional characteristics. The process of generating neurons from stem cells is called neurogenesis. One prominent example of a neural stem cell is the radial glial cell, so named because it has a distinctive bipolar morphology with highly elongated processes spanning the thickness of the neural tube wall, and because historically it shared some glial characteristics, most notably the expression of glial fibrillary acidic protein (GFAP).[11][12] The radial glial cell is the primary neural stem cell of the developing vertebrate CNS, and its cell body resides in the ventricular zone, adjacent to the developing ventricular system. Neural stem cells are committed to the neuronal lineages (neurons, astrocytes, and oligodendrocytes), and thus their potency is restricted.[10]

Nearly all research to date has made use of mouse embryonic stem cells (mES) or human embryonic stem cells (hES) derived from the early inner cell mass. Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin as an extracellular matrix (for support) and require the presence of leukemia inhibitory factor (LIF). Human ES cells are grown on a feeder layer of mouse embryonic fibroblasts (MEFs) and require the presence of basic fibroblast growth factor (bFGF or FGF-2).[13] Without optimal culture conditions or genetic manipulation,[14] embryonic stem cells will rapidly differentiate.

A human embryonic stem cell is also defined by the expression of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and Sox2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.[15] The cell surface antigens most commonly used to identify hES cells are the glycolipids stage specific embryonic antigen 3 and 4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. By using human embryonic stem cells to produce specialized cells like nerve cells or heart cells in the lab, scientists can gain access to adult human cells without taking tissue from patients. They can then study these specialized adult cells in detail to try and catch complications of diseases, or to study cells reactions to potentially new drugs. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.[16]

There are currently no approved treatments using embryonic stem cells. The first human trial was approved by the US Food and Drug Administration in January 2009.[17] However, the human trial was not initiated until October 13, 2010 in Atlanta for spinal cord injury research. On November 14, 2011 the company conducting the trial (Geron Corporation) announced that it will discontinue further development of its stem cell programs.[18] ES cells, being pluripotent cells, require specific signals for correct differentiationif injected directly into another body, ES cells will differentiate into many different types of cells, causing a teratoma. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face.[19] Due to ethical considerations, many nations currently have moratoria or limitations on either human ES cell research or the production of new human ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.

Human embryonic stem cell colony on mouse embryonic fibroblast feeder layer

The primitive stem cells located in the organs of fetuses are referred to as fetal stem cells.[20] There are two types of fetal stem cells:

Adult stem cells, also called somatic (from Greek , "of the body") stem cells, are stem cells which maintain and repair the tissue in which they are found.[22] They can be found in children, as well as adults.[23]

Pluripotent adult stem cells are rare and generally small in number, but they can be found in umbilical cord blood and other tissues.[24] Bone marrow is a rich source of adult stem cells,[25] which have been used in treating several conditions including liver cirrhosis,[26] chronic limb ischemia [27] and endstage heart failure.[28] The quantity of bone marrow stem cells declines with age and is greater in males than females during reproductive years.[29] Much adult stem cell research to date has aimed to characterize their potency and self-renewal capabilities.[30] DNA damage accumulates with age in both stem cells and the cells that comprise the stem cell environment. This accumulation is considered to be responsible, at least in part, for increasing stem cell dysfunction with aging (see DNA damage theory of aging).[31]

Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, dental pulp stem cell, etc.).[32][33]

Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants.[34] Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses.[35]

The use of adult stem cells in research and therapy is not as controversial as the use of embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Additionally, in instances where adult stem cells are obtained from the intended recipient (an autograft), the risk of rejection is essentially non-existent. Consequently, more US government funding is being provided for adult stem cell research.[36]

Multipotent stem cells are also found in amniotic fluid. These stem cells are very active, expand extensively without feeders and are not tumorigenic. Amniotic stem cells are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines.[37] Amniotic stem cells are a topic of active research.

Use of stem cells from amniotic fluid overcomes the ethical objections to using human embryos as a source of cells. Roman Catholic teaching forbids the use of embryonic stem cells in experimentation; accordingly, the Vatican newspaper "Osservatore Romano" called amniotic stem cells "the future of medicine".[38]

It is possible to collect amniotic stem cells for donors or for autologuous use: the first US amniotic stem cells bank [39][40] was opened in 2009 in Medford, MA, by Biocell Center Corporation[41][42][43] and collaborates with various hospitals and universities all over the world.[44]

These are not adult stem cells, but rather adult cells (e.g. epithelial cells) reprogrammed to give rise to pluripotent capabilities. Using genetic reprogramming with protein transcription factors, pluripotent stem cells equivalent to embryonic stem cells have been derived from human adult skin tissue.[45][46][47]Shinya Yamanaka and his colleagues at Kyoto University used the transcription factors Oct3/4, Sox2, c-Myc, and Klf4[45] in their experiments on human facial skin cells. Junying Yu, James Thomson, and their colleagues at the University of WisconsinMadison used a different set of factors, Oct4, Sox2, Nanog and Lin28,[45] and carried out their experiments using cells from human foreskin.

As a result of the success of these experiments, Ian Wilmut, who helped create the first cloned animal Dolly the Sheep, has announced that he will abandon somatic cell nuclear transfer as an avenue of research.[48]

Frozen blood samples can be used as a source of induced pluripotent stem cells, opening a new avenue for obtaining the valued cells.[49]

To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.[50]

An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in Drosophila germarium have identified the signals decapentaplegic and adherens junctions that prevent germarium stem cells from differentiating.[51][52]

Stem cell therapy is the use of stem cells to treat or prevent a disease or condition. Bone marrow transplant is a form of stem cell therapy that has been used for many years without controversy. No stem cell therapies other than bone marrow transplant are widely used.[53][54]

Stem cell treatments may require immunosuppression because of a requirement for radiation before the transplant to remove the person's previous cells, or because the patient's immune system may target the stem cells. One approach to avoid the second possibility is to use stem cells from the same patient who is being treated.

Pluripotency in certain stem cells could also make it difficult to obtain a specific cell type. It is also difficult to obtain the exact cell type needed, because not all cells in a population differentiate uniformly. Undifferentiated cells can create tissues other than desired types.[55]

Some stem cells form tumors after transplantation;[56] pluripotency is linked to tumor formation especially in embryonic stem cells, fetal proper stem cells, induced pluripotent stem cells. Fetal proper stem cells form tumors despite multipotency.[citation needed]

Some of the fundamental patents covering human embryonic stem cells are owned by the Wisconsin Alumni Research Foundation (WARF) they are patents 5,843,780, 6,200,806, and 7,029,913 invented by James A. Thomson. WARF does not enforce these patents against academic scientists, but does enforce them against companies.[57]

In 2006, a request for the US Patent and Trademark Office (USPTO) to re-examine the three patents was filed by the Public Patent Foundation on behalf of its client, the non-profit patent-watchdog group Consumer Watchdog (formerly the Foundation for Taxpayer and Consumer Rights).[57] In the re-examination process, which involves several rounds of discussion between the USTPO and the parties, the USPTO initially agreed with Consumer Watchdog and rejected all the claims in all three patents,[58] however in response, WARF amended the claims of all three patents to make them more narrow, and in 2008 the USPTO found the amended claims in all three patents to be patentable. The decision on one of the patents (7,029,913) was appealable, while the decisions on the other two were not.[59][60] Consumer Watchdog appealed the granting of the '913 patent to the USTPO's Board of Patent Appeals and Interferences (BPAI) which granted the appeal, and in 2010 the BPAI decided that the amended claims of the '913 patent were not patentable.[61] However, WARF was able to re-open prosecution of the case and did so, amending the claims of the '913 patent again to make them more narrow, and in January 2013 the amended claims were allowed.[62]

In July 2013, Consumer Watchdog announced that it would appeal the decision to allow the claims of the '913 patent to the US Court of Appeals for the Federal Circuit (CAFC), the federal appeals court that hears patent cases.[63] At a hearing in December 2013, the CAFC raised the question of whether Consumer Watchdog had legal standing to appeal; the case could not proceed until that issue was resolved.[64]

Diseases and conditions where stem cell treatment is being investigated include:

Research is underway to develop various sources for stem cells, and to apply stem cell treatments for neurodegenerative diseases and conditions, diabetes, heart disease, and other conditions.[80]

In more recent years, with the ability of scientists to isolate and culture embryonic stem cells, and with scientists' growing ability to create stem cells using somatic cell nuclear transfer and techniques to create induced pluripotent stem cells, controversy has crept in, both related to abortion politics and to human cloning.

Hepatotoxicity and drug-induced liver injury account for a substantial number of failures of new drugs in development and market withdrawal, highlighting the need for screening assays such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process.[81]

Link:
Stem cell - Wikipedia

The results of a quick and dirty research project on stem cell research studies.....

If I Google "stem cell clinical trials", I get several hundred thousand results... So, changing to "clinical trials stem cell COPD", I come up with several sites that claim to be experiencing fabulous success in stem cell therapy for COPD patients. Further study of these sites reveals that they all make a point that their procedures are not approved by the FDA, and that the only verifiable positive results are anecdotal, that is, from the statements of their own patients. All well and good, if the statements are true, and if the reports of their patients are not just the result of the placebo effect brought on by their desperate hope that the trials did in fact work.

In addition to these sites, there is one from the American Lung Association with quite a bit of information on the possibilities of stem cell therapy. Included in the ALA site is a link to:

http://www.clinicaltrials.gov/

which takes me to a listing of the hundreds of clinical trials currently under consideration, recruiting, or underway. There are also a few that have been completed. I urge you to take a look at the site. Once there, I searched for stem cells COPD, and came up with a list of 18 trials in various stages, most of which actually had something to do with COPD.

On the surface, the listing appeared to be just that; the information for various institutions that are seriously looking into the value of stem cells in the treatment of lung disease. And, hopefully, most of them are legitimate.

So, reading through the list, it appears that there are some trials going on, most of them in the US, having to do with stem cell therapy for COPD. However, further digging in at least a couple of the sites revealed the following:

One of the companies, on its web site, appears to me to claim that they are presently administering stem cell treatments, and that they have had success in relieving the symptoms and (at least so far), improving the prognosis of COPD patients. Again to me, that casts a bit of a cloud on the validity of the supposed trial.

Another of the companies talks a lot about various stem cell treatments, but does not mention anything related to COPD. So far, so good...but then, there it was! The information that they have a clinic in Mexico that deals in stem cell therapy for COPD.

Believe me when I say that nothing would make me happier than to discover that someone, somewhere, was having success in healing COPD patients, whether it was from stem cells or from dancing around them dressed in feathers. I fully realize the desperation of someone with a chronic disease. I have been there. However, I totally detest anyone who would take advantage of that desperation to extract money from the patients or their families.

Please be careful.

Uncle Jim

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Stem Cell Therapy for COPD

Stem Cell Therapy in Michigan

Thank you for visiting. Many people have been awaiting a practical way to get stem cells for various conditions. This site is intended to offer information so you can learn about current options, understand what stem cells are, and to allow you to determine if this stem cell therapy be for you.

The term Stem Cells refers to cells in your body that are lying dormant, and designed to regenerate or repair diseased tissues. Stem Cell Therapy refers to isolating and deploying stem cells into your body with the intention of regenerating the tissues they are designed to repair.

Your stem cells are your bodys natural healing cells. They are recruited by chemical signals emitted by damaged tissues to repair and regenerate your damaged cells. Stem cells derived from your own tissues may well be the next major advance in medicine. Allure Medical Spa has the technology to produce a solution rich with your own stem cells. Under investigational protocols these can be deployed to treat a number of degenerative conditions and diseases.

At this time, the cost of experimental stem cell treatments is not covered by insurance companies. We believe that our research is university quality. We are patient funded and we have no source of grants or pharmaceutical company funding. Although we are a for-profit organization, our goal is not to patent stem cell technology for corporate profit but rather to learn the medical potential of these cells and contribute to the science of regenerative medicine. We have set our fees very reasonably to lower the threshold of access to stem cell medicine. Our fee includes harvesting, isolating cells and deployment of your own cells. Also, under special conditions, your stem cells may be cryogenically stored for future treatments.

Read more:
Stem Cell Therapy Treatment at Allure Medical Spa in Michigan

Utilizing your own stem cells to help the healing process of injured or degenerated joints The human body is made of billions of specialized cells that form specific organs like the brain, skin, muscles, tendons, ligaments, joints, and bone. Each day these cells go through a degenerative and regenerative process. As older cells die, new cells are born from stem cells with the unique capability of being able to create multiple types of other cells. However, when tissues are injured, the degenerative process exceeds this regenerative process, resulting in structures that become weaker, painful and less functional. While there are several types of stem cells, those that are best at promoting musculoskeletal healing (tendon, ligament, cartilage and bone) are found in bone marrow. These mesenchymal stem cells, or MSCs, are essential to successful patient outcomes and at Stem Cell ARTS we utilize the patented Regenexx Stem Cell Protocol, which iscapable of yielding much higher concentrations of these important cells. Most Commonly Treated Knee Conditions and Injuries Below is a list of the most common knee injuries and conditions that we treat with stem cells or platelet procedures. This is not an all-inclusive list. Knee Patient Outcome Data

This Regenexx bone marrow derived stem cell treatment outcome data analysis is part of the Regenexx data download of patients who were tracked in the Regenexx advanced patient registry.

Regenexx has published more data on stem cell safety in peer reviewed medical research for orthopedic applications than any other group world-wide. This is a report of 1,591 patients and 1,949 procedures treated with the Regenexx Stem Cell Procedure. Based on our analysis of this treatment registry data, the Regenexx Stem Cell Procedure is about as safe as any typical injection procedure, which is consistent with what we see every day in the clinic.

To use, begin playing the first video. Then use the Playlist Dropdown Menu in the upper left corner of the video display to show all video titles. Use the Scroll Bar on the right hand side of the playlist to browse all video titles if required.

These non-surgical stem cell injection procedures happen within a single day and may offer a viable alternative for those who are facing surgery or even joint replacement. Patients are typically able to return to normal activity following the procedure and are able to avoid the painful and lengthy rehabilitation periods that are typically required to help restore strength, mobility and range-of-motion following invasive joint surgeries. Lastly, patients are far less vulnerable to the risks of surgeries, such as infection and blood clots.

Modern techniques in todays medicine allows us to withdraw stem cells from bone marrow, concentrate them through a lab process and then re-inject them precisely into the injured tissues in other areas of the body using advanced imaging guidance. Through Fluoroscopy and MSK Ultrasound, were able to ensure the cells are being introduced into the exact area of need. When the stem cells are re-injected, they enhance the natural repair process of degenerated and injured tendons, ligaments, and arthritic joints Turning the tables on the natural breakdown process that occurs from aging, overuse and injury.

If you are suffering from a joint injury or degenerative condition such as osteoarthritis, you may be a good candidate for a stem cell procedure. Please complete the form below and we will immediately send you an email with additional information and next steps in determining whether youre a candidate for these advanced stem cell procedures.

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Stem Cell Therapy for Knee Injuries and Arthritis - StemCell ARTS

Mayo Clin Proc. 2009 Oct; 84(10): 859861.

Regenerative Medicine Institute, National Centre for Biomedical Engineering Science, National University of Ireland, Galway

Stem cell therapy has recently progressed from the preclinical to the early clinical trial arena for a variety of disease states. Two review articles published in the current issue of Mayo Clinic Proceedings address the use of stem cells for cardiac repair and bone disorders.1,2 These articles provide state-of-the-art information regarding 2 important aspects of an exciting topic with wide-ranging therapeutic potential in a manner relevant to the Proceedings' core audience of practicing clinicians. Stem cell therapy is potentially applicable to all subspecialties of medicine, but both articles stress that caution is required in interpreting the current role of these technologies in medical practice.

The clinical need for new therapies for cardiac repair is obvious and particularly relevant to conditions such as heart failure, ischemic cardiomyopathy, and myocardial infarction (MI). Studies using cell therapies in humans with these conditions are performed rapidly after demonstration of efficacy in animal models. This progression has occurred without a clear understanding of the basic science underpinning this technology.

Most patients enrolled in clinical studies of cardiac repair using stem cell therapy have had an MI. The clinical rationale for stem cell therapy for MI is to restore cardiac function and thus prevent left ventricular remodeling that can lead to heart failure. Gersh et al1 report that these studies have demonstrated safety, with only modest improvement in cardiac function. Recent meta-analyses have confirmed modest improvements in left ventricular ejection fraction (LVEF) associated with cell therapy after MI.3,4 The findings of some studies have suggested that patients with the most severe MIs benefit the most, but a recent publication of the REGENT trial has shown no benefit from cell therapy, even in patients with LVEF of less than 40%.5 The REGENT trial may have been limited by inadequate power to detect a difference between the study and control groups, but contradictory results have also been observed in previous studies of intracoronary delivery of bone marrow-derived progenitor cells (ASTAMI and REPAIR-AMI).6,7 Substantial progress has been made in understanding the potential of cell therapy in cardiovascular disease, but there is still a dearth of crucial information, such as the optimal cell type; mode of processing of cells; and dose, mode, and timing of cell delivery. Most studies have used unfractionated or mononuclear bone marrow cells that were injected via catheters into the infarct-related artery within a few days of the MI. These limitations may be responsible for the inconsistent outcomes reported in human studies. It would appear that, in patients with preserved LVEF after MI, stem cell therapy provides no benefit, but those with large MIs and reduced LVEF may benefit. However, the modest efficacy outcomes are probably related to poor engraftment and retention of the injected cells in myocardium, issues that require additional preclinical experiments. Future studies should focus on patients with the largest infarcts and on methods to enhance engraftment of stem cells at the site of injury.

See also pages 876 and 893

In another study in the Proceedings, Undale et al2 review the therapeutic potential of stem cell therapy for bone repair and metabolic bone disease. This field is at an earlier stage than cell therapy for cardiac repair in that the numbers of patients studied are lower. These authors review human studies in nonunion of fractures, osteogenesis imperfecta, and hypophosphatasia. In contrast with most studies of cardiac repair in which mixed cell populations have been used, a single cell type, mesenchymal stem cells (MSCs), has been used in studies of bone repair. Although the nature of MSCs is beyond the scope of this editorial, this cell type has considerable potential for treatment of musculoskeletal disorders due to its ability to differentiate to bone and cartilage. In addition, MSCs can be expanded easily in culture and have immunosuppressive properties, which raises the possibility of allogeneic off-the-shelf treatments. Potential problems include culture expansion-induced karyotypic abnormalities, but this has not been observed in all studies.8,9

The current status of adult stem cell therapy could be summarized as having shown enormous potential in preclinical animal studies without the same degree of positive results in early human studies. This may be due to the fact that stem cells, despite their demonstrated resistance to hypoxia,10 have low survival rates at the disease site. Indeed, the relationship between therapeutic effect and numbers of cells administered is highlighted in the review by Undale at al. Genetic modification of stem cells and the use of biomaterial scaffolds to promote engraftment and enhance persistence at the disease site in animal models have augmented the therapeutic effect.11,12

Before stem cell therapy for tissue repair applications can progress, several important topics must be addressed thoroughly. First, the therapeutic mechanism of action needs to be defined. The early assumption was that differentiation of the transplanted cells gave rise to cells with a local phenotype that reconstituted or rebuilt damaged tissue, but little evidence supports this theory. It seems more likely that the concept of engineered tissue is not central to the mode of action and that the repair response depends rather on a dynamic and complex signaling network between the transplanted cells and host cells. This involves secretion of paracrine factors by the transplanted cells, and expression of these factors may be stimulated by the injured host environment.

Second, wide-ranging toxicology studies are needed to enhance our confidence in the use of cellular therapies. Although these therapies are generally considered safe, data on the long-term effects of cell transplant are still lacking. The possibility of tumorigenicity has been raised in a number of studies. For allogeneic transplant, these issues become even more important.

Third, proper standardization and characterization of transplanted cell preparations have not yet been achieved. This is a serious impediment to meaningful interpretation of the results of preclinical and early clinical studies. The issues of heterogeneity and phenotypic changes associated with expansion of MSCs must be addressed more satisfactorily before we can understand the full therapeutic potential of these cells.

Stem cell therapies have not yet become a routine component of clinical practice, but practicing physicians may be asked for advice by patients seeking cures for conditions for which conventional medicine offers no solution. Substantial numbers of patients are pursuing experimental stem cell treatments and in many cases are incurring considerable expense. Both review articles in this issue of Mayo Clinic Proceedings emphasize that stem cell research is at an early stage and that patients should be discouraged from undergoing a form of treatment whose safety and efficacy have not yet been proven.

As previously mentioned, it is vitally important to understand the mechanism underlying the potential benefits of stem cell administration so that new therapeutic paradigms may evolve. A large body of evidence suggests that the cell per se may not be required and that the mechanism of effect is paracrine in nature.13 For instance, MSCs secrete proangiogenic and cytoprotective factors that may be responsible for their therapeutic benefit.14 These paracrine factors may also activate host endogenous stem cells. Understanding the host-stem cell interaction may allow identification of novel therapeutic factors or pathways that can be modulated without the need for cell delivery.

Compared with the concept of paracrine effects, there is less evidence of therapeutic benefit related to differentiation of transplanted adult stem cells to host tissue, but this approach may be important in certain disease states. Future areas of research may focus on the need for differentiation vs paracrine effects to afford a specific therapeutic outcome. If therapeutic benefit depends on differentiation rather than paracrine effects, embryonic stem cells or the recently developed induced pluripotent stem cells may be the optimal choice.15 Although induced pluripotent stem cells lack the ethical problems associated with embryonic stem cells, they have substantial regulatory hurdles to surmount before introduction to the clinical realm because of the factors required for their generation and the risks of teratogenicity.

Stem cells may be considered one of the available tools in the evolving area of regenerative medicine. The goal of regenerative medicine is to promote organ repair and regeneration, thus obviating the need for replacement. Stem cell therapy may participate in this process via paracrine mechanisms or differentiation into native tissues. The target disease will probably influence which of these mechanisms is more important. Successful translation to the clinical realm will require an understanding of disease pathogenesis and stem cell biology and partnership with other disciplines such as medical device technology, biomaterials science, gene therapy, and transplantation immunology. Advanced hybrid technologies arising from such partnerships will represent the next generation of regenerative therapeutics and will assist in overcoming current barriers to clinical translation, such as poor rates of stem cell engraftment and persistence.

Stem cell therapies have demonstrated therapeutic efficacy and benefit in preclinical models, but results in clinical studies have not been impressive. For this reason, stem cell therapies remain in the realm of experimental medicine. The debate continues as to whether clinical trials are justified in the absence of a more complete understanding of the biology underpinning stem cell therapies. Basic science studies to understand the mechanism of effect and the biology of stem cell differentiation must continue.

However, carefully planned and ethically approved clinical trials resulting from a robust preclinical pathway are necessary to advance the field. This will require a programmatic approach that involves partnerships of clinicians, academics, industry, and regulatory authorities with a focus on understanding basic biology that informs a tight linkage between preclinical and clinical studies. Rather than suggesting that clinical trials are premature, such trials should be encouraged as part of multidisciplinary programs in regenerative medicine.

Articles from Mayo Clinic Proceedings are provided here courtesy of The Mayo Foundation for Medical Education and Research

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Stem Cell Therapy and Regenerative Medicine