StemCell Therapy

Humanity is currently facing a huge challenge imposed by the coronavirus. Borders are being shut down, planes grounded, and factories closed. At the same time, scientists and public health professionals are working on tests, treatments, and vaccines to soon provide a medical response. Coping with corona might be one of the largest tests humans have faced in the past decades but it wont be the last virus we need to defeat. It is time to embrace bioscience and allow more research and applications of genetic alteration methods.

For the layman, all this technobabble about mutagenesis and genetic engineering is difficult to comprehend and it took me personally a good amount of reading to start grasping what different methods exist and how these can massively improve our quality of life.

Lets first look at the four most common ways to alter the genes of a plant or animal:

This can be even done in grown humans that are alive, which is a blessing for everyone who suffers from genetic disorders. We are able to repair genes in live organisms. Gene editing is also thousands of times more accurate than just bombarding seeds with radiation. Some applied examples are deactivating the gene responsible for generating gluten in wheat: The result is gluten-free wheat. There are several methods that achieve this. One of the most popular ones these days is the so-called CRISPR Cas-9. These scissors are usually reprogrammed bacteria that transmit the new gene information or deactivate defunct or unwanted genes. Many science fiction novels and movies show a future in which we can deactivate genetic defects and cure humans from terrible diseases. Some examples of stories in which CRISPR-like techniques have been used are movies such as GATTACA, Star Treks Wrath of Khan, or the Expanse series in which gene editing plays a crucial role in growing crops in space.

Synthetic biologists have started usingCRISPR to synthetically create partsof the coronavirus in an attempt to launch a vaccine against this lung disease and be able to mass-produce it very quickly. In combination with computer simulations and artificial intelligence, the best design for such a vaccine is calculated on a computer and then synthetically created. This speeds up vaccine development and cuts it from years to merely months. Regulators and approval bodies have shown that in times of crisis they can also rapidly approve new testing and vaccination procedures which usually require years of back and forth with agencies such as the FDA?

CRISPR also allows the search for specific genes, also genes of a virus. This helped researchersto build fast and simple testing proceduresto test patients for corona.

In the long term, gene editing might allow us to increase the immunity of humans by altering our genes and making us more resistant to viruses and bacteria.

While the coronavirus seems to really test our modern society, we also need to be aware that this wont be the last pathogen that has the potential to kill millions. If we are unlucky, corona might mutate quickly and become harder to fight. The next dangerous virus, fungus, or bacteria is probably around the corner. Hence we need to embrace the latest inventions of biotechnology and not block genetic research and the deployment of its findings.

Right now a lot of red tape and even outright bans are standing between lifesaving innovations such as CRISPR and patients around the world. We need to rethink our hostility towards genetic engineering and embrace it. To be frank: We are in a constant struggle to fight newly occurring diseases and need to be able to deploy state of the art human answers to this.

Fred Roeder is a Health Economist from Germany and has worked in healthcare reform in North America, Europe, and several former Soviet Republics. One of his passions is to analyze how disruptive industries and technologies allow consumers more choice at a lower cost. Follow him on Twitter @FredCyrusRoeder

A version of this article was originally published at Consumer Choice Center and has been republished here with permission. The center can be found on Twitter @ConsumerChoiceC

See original here:
What comic book super heroes and villains tell us about plant and human gene editing and the coronavirus - Genetic Literacy Project

GGG>AAC changes in the SARS-CoV-2 have resulted in two types of strains with different infectivity as shown in the research of Dr. Mustak Ibn Ayub. These two strains can be further subdivided which helps to understand both infectivity and lethality of SARS-CoV-2 in different regions Courtesy

The observation sheds light on the association between Sars-CoV-2 mutations and its infectivity for the first time

Sars-CoV-2, the new strain of coronavirus behind the global Covid-19 pandemic, has changed in different countries by accumulating only a handful of key changes in its genome. Among them, a unique change has made the virus less infective, according to a research.

Dr Mustak Ibn Ayub, assistant professor at the department of genetic engineering and biotechnology at Dhaka University, discovered the unique change during his research of the virus' genetic mutations, according to a press statement.

A genome is the complete genetic information of any living entity that works as the blue print to determine its characteristics.

Dr Mustak, who obtained his PhD from Oxford University in the UK, characterized two strains of the virus after analyzing 3,000 complete genome sequences of Sars-CoV-2.

Designated as Sars-CoV-2a and Sars-CoV-2g, the strains have a unique difference in the 28,881-28,883 position of their genomes.

In Sars-CoV2g, those three positions are occupied by GGG, but in Sars-CoV2a, the GGG positions have mutated into AAC, the research findings show.

This is a unique event where three nucleotide (the building blocks of the virus genome) have changed as a bloc among 30,000 such positions in the virus genome.

Dr Mustak Ibn Ayub | CourtesyThe research also showed that this unique mutation negatively affects the nucleocapsid (N) protein, a crucial component for virus multiplication and infection of new cells.

The journal paper written based on the research is waiting peer review but has been published as a preprint here.

A remarkable finding in Dr Mustaks research is that the Sars-CoV-2a strain is prevalent in areas or countries with relatively low Covid-19 cases, such as Portugal, Netherlands, and Belgium, whereas in highly affected countries such as the US, Spain, France, and Germany, Sars-CoV-2g is predominant.

This trend is also true in different regions within a country, as shown in the research; Abruzzo in Italy has very low Covid-19 cases and high presence of Sars-CoV-2a.

This crucial observation sheds light on the association between Sars-CoV-2 mutations and its infectivity for the first time.

However, Dr Mustak cautioned that more studies need to be designed and executed on this aspect of Sars-CoV-2 mutation across the world.

He expects that from such research, monitoring the dynamics of these two strains will give valuable information to understand and manage the course of Covid-19 pandemic around the globe.

Read more here:
Coronavirus might be changing into less infective form, DU teacher's research finds - Dhaka Tribune

Since the beginning of the COVID-19 outbreak in December 2019, many hypotheses have been advanced to explain where the novel coronavirus (SARS-CoV-2) actually came from. Initial reports pointed to the Huanan seafood market in Wuhan, China, as the source of infection, however later studies called this into question. Given the uncertainty, many have suggested that a laboratory in Wuhan may be the actual source of the novel coronavirus. In this Insight article, we examine the three most widespread origin stories for the novel coronavirus, and examine the evidence for or against each proposed hypothesis. The hypotheses are listed in order from least likely to most likely, based on currently available evidence.

Although none of the individual pieces of evidence described below definitively identify the virus origin, the preponderance of evidence when taken together currently points to a natural origin with a subsequent zoonotic transmission from animals to humans, rather than a bioengineering or lab leak origin.

Hypothesis 1: The novel coronavirus is manmade, genetically engineered as bioweaponry or for health applications This hypothesis began circulating in February 2020. To date, it has been largely rejected by the scientific community. Some of the early claims have their roots in a preprint (a study in progress which has not been peer-reviewed or formally published) uploaded to ResearchGate by Chinese scientists Botao Xiao and Lei Xiao, who claimed that somebody was entangled with the evolution of 2019-nCoV coronavirus. In addition to origins of natural recombination and intermediate host, the killer coronavirus probably originated from a laboratory in Wuhan.

However, the only piece of evidence the authors provided to support their conclusion was the proximity of both the Wuhan Centers for Disease Control & Prevention and the Wuhan Institute of Virology (WIV) to the seafood market. The authors later withdrew their article, saying that their speculation about the possible origins was not supported by direct proofs. Copies of the original article can still be found online.

The withdrawal of the preprint did not stop this hypothesis from spreadinginstead it continued to grow in complexity, with some claiming that the virus showed signs of genetic engineering. Some of these claims were based on a preprint uploaded to BioRxiv, purporting to show that genetic material from the human immunodeficiency virus (HIV) had been inserted into the novel coronavirus.

This study was found to have significant flaws in design and execution and was also later withdrawn, as reported in our review explaining that No, HIV insertions were not identified in the 2019 coronavirus. However, the poor quality of the preprint did not prevent this baseless speculation from being promoted by blogs such as Zero Hedge, Infowars, Natural News, and even some scientists like Luc Montagnier, a French virologist who co-discovered HIV, but has recently become a promoter of numerous unsupported theories.

Indeed, scientists who examined the preprint highlighted that these so-called insertions are very short genetic sequences which are also present in many other life forms, such as the bacterium Magnetospirillum magnetotacticum, the spider Araneus ventricosus, and the parasites Cryptosporidium and Plasmodium malariae, which cause cryptosporidiosis and malaria, respectively[1,2]. Trevor Bedford, virologist at Fred Hutchinson Cancer Research Center and professor at the University of Washington, explained on Twitter that a simple BLAST of such short sequences shows [a] match to a huge variety of organisms. No reason to conclude HIV. [] These inserts are nothing of the sort proposed by the paper and instead arose naturally in the ancestral bat virus.

In other words, the sequences analyzed by the study authors were so short that it is easy to find similarities to a wide variety of organisms, including HIV. An analogy would be to search for a short and commonly-used word, like sky, in a search engine and claim that the search results show content that is identical or similar to each other solely because of that one word.

Another version of the engineered-virus story stated that a pShuttle-SN sequence is present in the novel coronavirus. The pShuttle-SN vector was used during efforts to develop candidates for a SARS vaccine[3] and was therefore used to support claims of human engineering. These claims appeared in blogs such as Infowars, Natural News, and The Epoch Times. However, analysis of the genomic sequence of the novel coronavirus showed that no such man-made sequence was present, as reported in our review.

Other claims regarding the purported manmade origins of the virus have linked it to bioweapons research. These have appeared in articles such as a 22 February 2020 story by the New York Post, which we also reviewed and scientists found to be of low scientific credibility. The article provided no evidence that the novel coronavirus is linked to bioweapons research.

On 17 March 2020, a group of scientists published findings from a genomic analysis of the novel coronavirus in Nature Medicine[4], which established that SARS-CoV-2 is of natural origin, likely originating in pangolins or bats (or both) and later developing the ability to infect humans. Their investigation focused mainly on the so-called spike (S) protein, which is located on the surface of the enveloping membrane of SARS-CoV-2. The S protein allows the virus to bind to and infect animal cells. After the 2003-2005 SARS outbreak, researchers identified a set of key amino acids within the S protein which give SARS-CoV-1 a super-affinity for the ACE2 target receptor located on the surface of human cells[5,6].

Surprisingly, the S protein of SARS-CoV-2 does not contain this optimal set of amino acids[4], yet is nonetheless able to bind ACE2 with a greater affinity than SARS-CoV-1[7]. Taken together, these findings strongly suggest that SARS-CoV-2 evolved independently of human intervention and undermine the claim that it was manmade[1]. This is because if scientists had attempted to engineer improved ACE2 binding in a coronavirus, the best strategy would have been to harness the already-known and efficient amino acid sequences described in SARS-CoV-1 in order to produce a more optimal molecular design for SARS-CoV-2. The authors of the Nature Medicine study[4] concluded that Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus.

In summary, the hypothesis that the virus is manmade or engineered in any way is unsupported and inconsistent with available evidence, leading Bedford to assess the probability of this hypothesis being correct as extremely unlikely. Kristian Andersen, professor at the Scripps in San Diego declared during an online seminar, I know there has been a lot of talk about Chinese bioweapons, bioengineering, and engineering in general. All of that, I can say, is fully inconsistent with the data.

Like Andersen, other scientists have repeatedly explained that there is no evidence to support the claim that the virus was human engineered. In a statement published on 19 February in The Lancet, 27 eminent public health scientists in the U.S., Europe, the U.K., Australia, and Asia cited numerous studies from multiple countries which overwhelmingly conclude that this coronavirus originated in wildlife[8-15] as have so many other emerging pathogens.

[Back to top]

Hypothesis 2: The novel coronavirus is a natural virus that was being studied in the lab, from which it was accidentally or deliberately released Many have pointed out that even though the virus was unlikely engineered, it still might have been purposely or accidentally released from a lab. Claims about a possible laboratory release often point to a laboratory in China as the source, more specifically the Wuhan Institute of Virology (WIV), given that one of its laboratories studies bat coronaviruses. Similarly speculative claims have also implicated laboratories in the U.S. and Canada.

However, there is no evidence in either scientific publications or public announcements indicating that a virus resembling SARS-CoV-2 had been studied or cultured in any lab prior to the outbreak. While this of course does not rule out the possibility that scientists were working on it in secret, as of today, this claim is speculative and unsupported by evidence.

A January 2020 study in The Lancet, which found that about one-third of the initial round of infections had no connection to the Huanan seafood market[15], has been suggested as evidence that the virus may have leaked from a nearby lab. Richard Ebright, a professor of chemical biology at Rutgers, said in this CNN article:

It is absolutely clear the market had no connection with the origin of the outbreak virus, and, instead, only was involved in amplification of an outbreak that had started elsewhere in Wuhan almost a full month earlier.

Ebright also told CNN that The possibility that the virus entered humans through a laboratory accident cannot and should not be dismissed.

Nikolai Petrovsky, a professor at Flinders University who specializes in vaccine development, also supported the hypothesis that the virus could have escaped from a lab. In this article, he stated that no corresponding virus has been found to exist in nature and cited as-yet unpublished work, saying that the hypothesis is absolutely plausible. Petrovsky suggested that the virus could have escaped [the biosecure facility in Wuhan] either through accidental infection of a staff member who then visited the fish market several blocks away and there infected others, or by inappropriate disposal of waste from the facility that either infected humans outside the facility directly or via a susceptible vector such as a stray cat that then frequented the market and resulted in transmission there to humans.

Some have argued that instead of originating in nature, the virus could have been generated through simulated evolution in the lab. Christian Stevens, from the Benhur Lee lab at the Mount Sinai School of Medicine, explained in this article the extreme unlikelihood of this scenario.

Briefly, the mutations in the receptor-binding domain (RBD) of the S protein in SARS-CoV-2 resembles that of some pangolin coronaviruses. These mutations are also what make SARS-CoV-2 much better at infecting humans compared to SARS-CoV-1. Such mutations could be evolved in the lab through simulated evolution, however the likelihood of simulated natural selection stumbling on the near exact RBD from a previously unknown pangolin coronavirus is mathematically unlikely, said Stevens.

Furthermore, scientists would have had to know about these mutations in the S protein of some pangolin coronaviruses before the outbreak, and then tried to evolve a bat coronavirus with the same characteristics through animal experiments. As these mutations in pangolin coronaviruses were not identified until after the outbreak[16], it does not make sense for scientists to have performed such experiments in the lab, as there would have been little to no scientific justification for doing so.

Other considerations are the polybasic cleavage site and the O-linked glycan additions to the S protein, which have not been identified in bat betacoronaviruses nor the pangolin betacoronaviruses sampled so far. However, evidence indicates that these features are much more likely to have arisen in the presence of an immune system, suggesting that this is a natural adaptation by the virus to a live host, either an animal or a human. Because lab-based cell cultures do not have immune systems, Stevens explained that it is extremely unlikely that the virus would have developed such features using cell culture approaches, thereby undermining the lab-generated claims that some have proposed.

What about using animal models for evolution, which would provide selective pressure from an immune system? Stevens also examined this possibility and explained that there is no known animal model that would allow for selection of human-like ACE2 binding and avoidance of immune recognition. This strongly suggests that SARS-CoV-2 could not have been developed in a lab, even by a system of simulated natural selection.

In other words, the overall combination of features observed in SARS-CoV-2 is extremely unlikely to have arisen through experiments, even simulated evolution, because the experimental tools are not available at the moment.

Zhengli Shi, the head of the laboratory studying bat coronaviruses at the WIV, clarified in a Scientific American report published on 11 March, that during the early days of the outbreak, she had her team check the genome sequence of SARS-CoV-2 against the bat coronavirus strains being studied in her lab to ensure that the outbreak had not resulted from any mishandling of experimental materials, especially during disposal. They found that none of the sequences matched those of the viruses her team had sampled from bat caves.

However, this testimony has not satisfied those who allege a cover-up of a lab accident due to inadequate biosecurity, intentional release, or plain carelessness. Recent opinion pieces published by the Washington Postone on 2 April 2020 and another on 14 April 2020have also fueled speculation that the virus was accidentally released from a laboratory at the WIV due to biosafety lapses reportedly documented in diplomatic cables from 2018. The authors of these opinion pieces were careful to distance themselves from earlier claims that the coronavirus was bioengineered or resulted from deliberate wrongdoing, as one author stated. In any event, the accidental release scenario is currently being considered by scientists and U.S. intelligence and national security officials.

Indeed, despite safeguards, laboratory accidents can and do occur, and some have even caused outbreaks. In 2007, an outbreak of hand-foot-mouth (HFM) disease among livestock in the U.K. was linked to a faulty gas valve connected to labs involved in researching and producing HFM vaccines. And in 2004, a re-emergence of SARS occurred in Beijing, China, as a result of two lab accidents.

In an article published on 6 April, experts expressed skepticism at the lab leak hypothesis. Vincent Racaniello, a professor of virology at Columbia University, said I think it has no credibility. And Simon Anthony, an assistant professor at Columbia who studies the ecology and evolution of viruses, stated, it all feels far-fetched [] Lab accidents do happen, we know that, but [] theres certainly no evidence to support that theory.

In an April 10th article, Amesh Adalja from Johns Hopkins University Center for Health Security stated that he thought the lab leak hypothesis had a lower probability than the pure zoonotic theory. I think as we get a better understanding of where the origin of this virus was, and get closer to patient zero, that will explain some of the mystery. Bill Hanage, associate professor at the Harvard T.H. Chan School of Public Health, said If there is evidence to really support this theory beyond the coincidence of the location of the lab, then I havent seen it, and I dont make decisions on the basis of coincidence.

Several scientists have taken to Twitter to ponder the lab leak hypothesis made by the Washington Post opinion articles:

Overall, we have virus group, molecular features, market association, and environmental samples all pointing strongly towards zoonosis. The location in Wuhan is the only thing at all suggestive of lab escape. I see strength of evidence entirely for zoonosis.

Trevor Bedford

We dont know how this virus emerged, but all evidence points to spillover from its natural reservoir, whether that be a bat or some other intermediate species, pangolins or otherwise. Pushing this unsupported accident theory hinders efforts to actually determine virus origin.

Angela Rasmussen

The bottom line is that those vague diplomatic cables do not provide any specific information suggesting that [SARS-CoV-2] emerged from incompetence or poor biosafety protocols or anything else.

Angela Rasmussen [referencing the 14 April Washington Post opinion piece]

Most likely either 1) virus evolved to its current pathogenic state via a non-human host and then jumped to humans, or 2) a non-pathogenic version of the virus jumped from an animal into humans then evolved to a pathogenic state.

Josh Michaud

All current data supports that the ancestral station strain of the virus is in batsthey serve as the zoonotic reservoir. Then a spillover event occured into humans, perhaps aided by another mammal, although thats debatable.

Ryan McNamara

There is strong evidence that the #SARSCoV2 #coronavirus is NOT an engineered bioweapon.

That said, its important to be upfront that we do not have sufficient evidence to exclude entirely the possibility that it escaped from a research lab doing gain of function experiments.

Carl T. Bergstrom

In summary, the hypothesis that the virus escaped from a lab is supported largely by circumstantial evidence and is not supported by genomic analyses and publicly available information. In the absence of evidence for or against an accidental lab leak, one cannot rule it out as the actual source of the outbreak. I dont think we have real data to say when these things began, in large part because the data are being held back from inspection, said Gerald Keusch, associate director of the Boston University National Emerging Infectious Diseases Laboratories, in this LiveScience article.

Given allegations of a cover-up, it appears that only an open and transparent review of the laboratory activities at WIV can allow us to confirm or reject this unlikely hypothesis.

[Back to top]

Hypothesis 3: The novel coronavirus evolved naturally and the outbreak began through zoonotic infection Virologists explain that the most likely hypothesis is that the outbreak started with a naturally-occurring zoonotic infectionone that is transmitted from animals to humansrather than a lab breach. This is largely due to what we know of the virus genomic features, which strongly indicate a natural origin. For example, if a virus had escaped from a laboratory, its genome would likely be most similar to those of the viral strains cultured in that lab. However, as shown in this phylogenetic tree by Bedford (see figure below), SARS-CoV-2 does not cluster in the same branch as the SARS-like coronavirus WIV1 (WIV1) and SARS-CoV-1, which are commonly cultured lab strains with the closest similarity to SARS-CoV-2 at the WIV facility, which is the lab that some have suggested might be a potential source of a lab leak. Instead, SARS-CoV-2 aligns most closely with coronaviruses isolated in the wild from bats and pangolins, indicating that it is more likely to have come from a natural source than from a lab:

FigurePhylogenetic tree showing evolutionary relationships between different coronavirusesmostly bat coronaviruses and some pangolin coronaviruses (by Trevor Bedford). Different lab strains of SARS-CoV-1 (referred to as SARS-CoV here) are represented by yellow dots. WIV1, another common lab strain, is indicated with a black arrow.

Furthermore, SARS-CoV-2 displays evolutionary features which suggest that the virus originated in animals and jumped to humans. The closest sequenced ancestor of SARS-CoV-2 is RaTG13, a bat coronavirus with about 96% genome sequence identity[8]. But SARS-CoV-2 also has features that distinguish it from RaTG13 and other SARS-like coronaviruses including SARS-CoV-1. As mentioned in the previous section, these features are: mutations in the receptor binding domain (RBD) of the S protein, a polybasic cleavage site, and a nearby O-linked glycan addition site in the S protein[4]. The mutations in the RBD of the S protein resemble those of some pangolin coronaviruses, suggesting that the virus made a jump from bats to an intermediate (perhaps pangolins), and then later to humans.

To briefly re-cap from the previous section discussing the hypothesis of a lab origin, Christian Stevens explained in this article that the polybasic cleavage site and the O-linked glycan additions to the S protein have not been identified in bat betacoronaviruses nor the pangolin betacoronaviruses sampled so far. However, evidence indicates that these features are much more likely to have arisen in the presence of an immune system, suggesting that this is a natural adaptation by the virus to a live host, either an animal or a human.

And again, there is no known animal model that would allow for selection of human-like ACE2 binding and avoidance of immune recognition, Stevens explained. This strongly suggests that SARS-CoV-2 could not have been developed in a lab, even by a system of simulated natural selection. In other words, the overall combination of features observed in SARS-CoV-2 is extremely unlikely to have arisen through experiments, even simulated evolution, because the experimental tools are not available at the moment.

Finally, Christian Stevens highlighted that the Ka/Ks ratio of the virus strongly indicates that the virus did not come from lab-simulated evolution. The Ka/Ks ratio calculates the level of synonymous mutations (which do not produce any functional change in proteins) and non-synonymous mutations (which produce functional changes in proteins). Non-synonymous mutations are more likely to occur in the presence of selective pressure, such as a need to adapt to a new environment:

Because synonymous mutations should have no effect, we expect them to happen at a relatively consistent rate. That makes them a good baseline that we can compare the number of non-synonymous mutations to. By calculating the ratio between these two numbers we can differentiate between three different types of selection:

We would expect a virus that is learning to exist in a new context would be undergoing Darwinian selection and we would see a high rate of non-synonymous changes in some part of the genome. This would be the case if the virus were being designed via simulated natural selection, we would expect at least some part of the genome to show Darwinian selection.

An analysis by Bedford demonstrates that the level of non-synonymous mutations between SARS-CoV-2 and the naturally occurring RaTG13 are highly similar, standing at 14.3% and 14.2%, respectively.

Both of these numbers indicate a purifying selection, with very few non-synonymous changes. This holds true across the entire genome with no part of it showing Darwinian selection. This is a very strong indicator that SARS-CoV-2 was not designed using forced selection in a lab, Stevens concluded.

[Back to top]

Conclusions Taken together, the information presented here suggests that it is much more likely that SARS-CoV-2 was generated naturally and transmitted zoonotically, without any engineering or lab growth. Especially given the fact that the prior probability for the zoonotic hypothesis is high. Indeed, zoonotic infections (transmission of pathogens from animals/insects to humans) are not only plausible but common throughout the world, and have also caused outbreaks in the past. For example, the SARS outbreak, which began in 2002, was linked to civet cats. Outbreaks of Middle East respiratory syndrome have been linked to contact with camels. Nipah virus infection has been linked to fruit bats and caused outbreaks in Asia. Mosquitoes transmit viruses such as Zika, dengue, and chikungunya, while ticks also carry a range of pathogens, such as Lyme disease and Rocky Mountain spotted fever. In fact, according to the World Health Organization, about 60% of emerging diseases are zoonotic infections.

In summary, the hypothesis that the virus escaped from a lab is supported largely by circumstantial evidence and is not supported by publicly available information. In the case of the hypothesis that the outbreak began with zoonotic infection, at the moment genomic analyses are consistent with a natural origin for the virus and support the idea that the outbreak began zoonotically. Unlike the manmade virus and lab escape hypotheses, there is no compelling evidence against the hypothesis for natural zoonosis. As Stevens concluded, the hypothesis for natural zoonosis is the one that fits all available evidence, is most parsimonious, and best satisfies the concept of Occams Razorthat the simplest solution is most likely the right one.

[Back to top]

Christian Stevens from the Benhur Lee lab at the Mount Sinai School of Medicine has provided a comprehensive explanation of the multiple scientific studies examining the origin of the coronavirus.

Scientists explained in this 23 April NPR article why they found the lab accident hypothesis unlikely. In fact, the article states that there is virtually no chance that the new coronavirus was released as result of a laboratory accident in China or anywhere else.

Read the original here:
Did the COVID-19 virus originate from a lab or nature? Examining the evidence for different hypotheses of the novel coronavirus' origins - Health...

There has beenno scientific findingthat the novel coronavirus was bioengineered, but its origins are not entirely clear. Deadly pathogens discovered in the wild are sometimesstudied inlabs and sometimes made more dangerous. That possibility, and other plausible scenarios, have been incorrectly dismissed in remarks by some scientists andgovernment officials, and in the coverage of most major media outlets.

Regardless of the source of this pandemic, there is considerable documentation that a global biological arms race going on outside of public view could produce even more deadly pandemics in the future.

While much of the media and political establishment have minimized the threat from such lab work, some hawks on the American right like Sen. Tom Cotton, R-Ark., have singled outChinese biodefense researchers as uniquely dangerous.

But there is every indication that U.S. lab work is every bit as threatening as that in Chinese labs. American labs also operate insecret, and are also known to beaccident-prone.

The current dynamics of the biological arms race have been driven by U.S. government decisions that extend back decades. In December 2009, Reuters reported that the Obama administration was refusing even to negotiate the possible monitoring of biological weapons.

Advertisement:

Much of the left in the U.S. now appears unwilling to scrutinize the origin of the pandemic or the wider issue of biowarfare perhaps because portions of the anti-Chinese right have been sovocal in making unfoundedallegations.

Governments that participate in such biological weapon research generally distinguish between "biowarfare" and "biodefense," as if to paint such "defense" programs as necessary. But this is rhetorical sleight-of-hand; the two concepts are largely indistinguishable.

"Biodefense" implies tacit biowarfare, breeding more dangerous pathogens for the alleged purposeof finding a way tofightthem. While this work appears to have succeeded in creating deadly and infectious agents, including deadlier flu strains, such "defense" research is impotent in its ability to defend us from this pandemic.

The legal scholar who drafted the main U.S. law on the subject, Francis Boyle, warned in his 2005 book "Biowarfare and Terrorism" that an "illegal biological arms race with potentially catastrophic consequences" was underway, largely driven by the U.S. government.

For years,many scientistshave raised concerns regarding bioweapons/biodefense lab work, and specifically aboutthe fact that huge increases in funding have taken place since 9/11. This was especially true afterthe anthrax-by-mail attacks that killed five people in the weeks after 9/11, which the FBI ultimately blamed on a U.S. government biodefense scientist.A 2013 study found that biodefense funding since2001 hadtotaled at least $78 billion, and more has surely been spent since then. This has led to aproliferation of laboratories, scientists and new organisms, effectively setting off a biological arms race.

Following the Ebola outbreak in west Africa in 2014, the U.S. governmentpaused fundingfor what are known as "gain-of-function" research on certain organisms. This work actually seeks to make deadly pathogensdeadlier, in some cases making pathogens airborne thatpreviously were not. With little notice outside the field, the pause on such research was lifted in late 2017.

During this pause, exceptions for funding were made for dangerous gain-of-function lab work. This included work jointly done by U.S. scientists from the University of North Carolina, Harvard and the Wuhan Institute of Virology. This work which had funding from USAID and EcoHealth Alliance not originally acknowledged was published in2015 in Nature Medicine.

A different Nature Medicine article about the origin of the current pandemic,authored by five scientists andpublished on March 17,has been touted by major media outlet and some officials including current National Institutes of Health directorFrancis Collins as definitively disproving a lab origin for the novel coronavirus. That journal article, titled "The proximal origin of SARS-CoV-2," stated unequivocally: "Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus." This is a subtly misleading sentence. While the scientists state that there is no known laboratory "signature" in the SARS-Cov-2 RNA, their argument fails to take account of other lab methods that could have created coronavirus mutations without leaving such a signature.

Indeed, there is also thequestion of conflict of interest in the Nature Medicine article. Some of the authors of that article, as well as aFebruary 2020Lancet letter condemning "conspiracy theories suggesting that COVID-19 does not have a natural origin" which seemed calculated to minimize outside scrutiny of biodefense lab work have troubling ties to thebiodefense complex,as well as to the U.S. government. Notably, neither of these articles makes clear that a virus can have a natural originand then be captured and studied in a controlled laboratory setting before being let loose, either intentionally or accidentallywhichis clearly a possibility in the case of the coronavirus.

Facts as "rumors"

This reporter raised questions about the subject at a news conference with a Center for Disease Control (CDC) representative at the now-shuttered National Press Club on Feb. 11. I asked if it was a "complete coincidence" that the pandemic had started in Wuhan, the only place in China with a declared biosafety level 4 (BSL4) laboratory. BSL4 laboratories have the most stringent safety mechanisms, but handle the most deadly pathogens. As I mentioned, it was oddthat the ostensible origin of the novel coronavirus was bat caves in Yunnan province more than 1,000 miles from Wuhan. I noted that "gain-of-function" lab work can results in more deadly pathogens, and that major labs, including some in the U.S., have had accidental releases.

CDC Principal Deputy Director Anne Schuchat saidthatbased on the information she had seen, the virus was of "zoonotic origin." She also stated, regarding gain-of-function lab work, that it is important to "protect researchers and their laboratory workers as well as the community around them and that we use science for the benefit of people."

I followed up by asking whether an alleged natural origin did not preclude the possibility that this virus came through a lab, since a lab could have acquired a bat virus and been working on it. Schuchat replied to the assembled journalists that "it is very common for rumors to emerge that can take on life of their own," but did not directly answer the question. She noted that in the 2014 Ebola outbreak some observers had pointed to nearby labs as the possible cause, claiming this "was a key rumor that had to be overcome in order to help control the outbreak." She reiterated: "So based on everything that I know right now, I can tell you the circumstances of the origin really look like animals-to-human. But your question, I heard."

This is no rumor. It's a fact: Labs work with dangerous pathogens. The U.S. and China each have dual-use biowarfare/biodefense programs. China has major facilities at Wuhan a biosafety level 4 lab and a biosafety level 2 lab. There are leaks from labs. (See "Preventing a Biological Arms Race," MIT Press, 1990, edited by Susan Wright; also, a partial review in Journal of International Law from October 1992.)

Much of the discussion of this deadly serious subject is marred with snark that avoids or dodges the "gain-of-function" question. ABC ran a story on March 27 titled "Sorry, Conspiracy Theorists. Study Concludes COVID-19 'Is Not a Laboratory Construct.'" That story did not address the possibility that the virus could have been found in the wild, studied in a lab and thenreleased.

On March 21, USA Today published a piece headlined "Fact Check: Did the Coronavirus Originate In a Chinese Laboratory?" and rated it "FALSE."

That USA Today story relied on the Washington Post, which publishedawidely cited article onFeb.17headlined,"Tom Cotton keeps repeating a coronavirus conspiracy theory that was already debunked." That article quoted public comments fromRutgers University professor of chemical biology Richard Ebright, but out of context and only in part. Specifically, the story quoted from Ebright's tweet that the coronavirus was not an "engineered bioweapon." In fact, his full quote included the clarification that the virus could have "entered human population through lab accident." (An email requesting clarification sent toPost reporterPaulina Firoziwas met with silence.)

Bioengineered From a lab

Other pieces in the Post since then (some heavily sourced to U.S. government officials) have conveyed Ebright's thinking, but it gets worse. In a private exchange, Ebright who, again, has said clearly that the novel coronavirus was not technically bioengineered using known coronavirus sequences stated that other forms of lab manipulation could have beenresponsible for the current pandemic. This runs counter to much reporting, which is perhaps too scientifically illiterate to perceive the difference.

In response to the suggestion that the novel coronavirus could have come about through various methodsbesides bioengineering made by Dr. Meryl Nass, who has done groundbreaking work on biowarfareEbright responded in an email:

The genome sequence of SARS-CoV-2 has no signatures of human manipulation.

This rules out the kinds of gain-of-function (GoF) research that leave signatures of human manipulation in genome sequences (e.g., use of recombinant DNA methods to construct chimeric viruses), but does not rule out kinds of GoF research that do not leave signatures (e.g., serial passage in animals). [emphasis added]

Very easy to imagine the equivalent of the Fouchier's "10 passages in ferrets" with H5N1 influenza virus, but, in this case, with 10 passages in non-human primates with bat coronavirus RaTG13 or bat coronavirus KP876546.

That last paragraph is very important. It refersto virologist Ron Fouchier of the Erasmus Medical Center in Rotterdam, who performed research on intentionally increasing rates of viralmutation rate by spreading a virus from one animal to another in a sequence.The New York Times wrote about this in an editorial in January 2012, warning of "An Engineered Doomsday."

"Now scientists financed by the National Institutes of Health" have created a "virus that could kill tens or hundreds of millions of people" if it escaped confinement, the Times wrote. The story continued:

Working with ferrets, the animal that is most like humans in responding to influenza, the researchers found that a mere five genetic mutations allowed the virus to spread through the air from one ferret to another while maintaining its lethality. A separate study at the University of Wisconsin, about which little is known publicly, produced a virus that is thought to be less virulent.

The word "engineering" in the New York Times headline is technically incorrect, sincepassing a virus through animals is not "genetic engineering." This same distinction has hindered some from understanding the possible origins of the current pandemic.

Fouchier's flu work, in which an H5N1 virus was made more virulent by transmitting it repeatedly between individual ferrets, briefly sent shockwaves through the media. "Locked up in the bowels of the medical faculty building here and accessible to only a handful of scientists lies a man-made flu virus that could change world history if it were ever set free," wrote Science magazine in 2011 in a story titled "Scientists Brace for Media Storm Around Controversial Flu Studies." It continues:

The virus is an H5N1 avian influenza strain that has been genetically altered and is now easily transmissible between ferrets, the animals that most closely mimic the human response to flu. Scientists believe it's likely that the pathogen, if it emerged in nature or were released, would trigger an influenza pandemic, quite possibly with many millions of deaths.

In a 17th floor office in the same building, virologist Ron Fouchier of Erasmus Medical Center calmly explains why his team created what he says is "probably one of the most dangerous viruses you can make" and why he wants to publish a paper describing how they did it. Fouchier is also bracing for a media storm. After he talked to ScienceInsider yesterday, he had an appointment with an institutional press officer to chart a communication strategy.

Fouchier's paper is one of two studies that have triggered an intense debate about the limits of scientific freedom and that could portend changes in the way U.S. researchers handle so-called dual-use research: studies that have a potential public health benefit but could also be useful for nefarious purposes like biowarfare or bioterrorism.

Despite objections, Fouchier's article was published by Science in June 2012. Titled "Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets," it summarized how Fouchier's research team made the pathogen more virulent:

Highly pathogenic avian influenza A/H5N1 virus can cause morbidity and mortality in humans but thus far has not acquired the ability to be transmitted by aerosol or respiratory droplet ("airborne transmission") between humans. To address the concern that the virus could acquire this ability under natural conditions, we genetically modified A/H5N1 virus by site-directed mutagenesis and subsequent serial passage in ferrets. The genetically modified A/H5N1 virus acquired mutations during passage in ferrets, ultimately becoming airborne transmissible in ferrets.

In other words, Fouchier's research took a flu virus that did not exhibit airborne transmission, then infected a number of ferrets until it mutated to the point that it was transmissible by air.

In thatsame year, 2012, asimilar studyby Yoshihiro Kawaoka of the University of Wisconsin was published in Nature:

Highly pathogenic avian H5N1 influenza A viruses occasionally infect humans, but currently do not transmit efficiently among humans. ... Here we assess the molecular changes ... that would allow a virus ... to be transmissible among mammals. We identified a ... virus ... with four mutations and the remaining seven gene segments from a 2009 pandemic H1N1 virus that was capable of droplet transmission in a ferret model.

In 2014, Marc Lipsitch of Harvard and Alison P. Galvani of Yale wrote regarding Fouchier and Kawaoka's work:

Recent experiments that create novel, highly virulent and transmissible pathogens against which there is no human immunity are unethical ... they impose a risk of accidental and deliberate release that, if it led to extensive spread of the new agent, could cost many lives. While such a release is unlikely in a specific laboratory conducting research under strict biosafety procedures, even a low likelihood should be taken seriously, given the scale of destruction if such an unlikely event were to occur. Furthermore, the likelihood of risk is multiplied as the number of laboratories conducting such research increases around the globe.

Given this risk, ethical principles, such as those embodied in the Nuremberg Code, dictate that such experiments would be permissible only if they provide humanitarian benefits commensurate with the risk, and if these benefits cannot be achieved by less risky means.

We argue that the two main benefits claimed for these experiments improved vaccine design and improved interpretation of surveillance are unlikely to be achieved by the creation of potential pandemic pathogens (PPP), often termed "gain-of-function" (GOF) experiments.

There may be a widespread notion that there is scientific consensus that the pandemic did not come out of a lab. But in factmany of the most knowledgeable scientists in the field are notably silent. This includes Lipsitch at Harvard, Jonathan A. King at MITand many others.

Just last year, Lynn Klotz of the Center for Arms Control and Non-Proliferation wrote a paperin the Bulletin of the Atomic Scientistsentitled "Human Error in High-biocontainment Labs: A Likely Pandemic Threat." Wrote Klotz:

Incidents causing potential exposures to pathogens occur frequently in the high security laboratories often known by their acronyms, BSL3 (Biosafety Level 3) and BSL4. Lab incidents that lead to undetected or unreported laboratory-acquired infections can lead to the release of a disease into the community outside the lab; lab workers with such infections will leave work carrying the pathogen with them. If the agent involved were a potential pandemic pathogen, such a community release could lead to a worldwide pandemic with many fatalities. Of greatest concern is a release of a lab-created, mammalian-airborne-transmissible, highly pathogenic avian influenza virus, such as the airborne-transmissible H5N1 viruses created in the laboratories of Ron Fouchier in the Netherlands and Yoshihiro Kawaoka in Madison, Wisconsin.

"Crazy, dangerous"

Boyle, a professor of international law at the University of Illinois, has condemned Fouchier, Kawaoka and others including at least one of the authors of the recent Nature Medicine article in the strongest terms, calling such work a "criminal enterprise." While Boyle has been embroiled in numerous controversies, he's been especially dismissed by many on this issue. The "fact-checking" websiteSnopeshas described him as "a lawyer with no formal training in virology" without noting that he wrote the relevant U.S. law.

As Boyle saidin 2015:

Since September 11, 2001, we have spent around $100 billion on biological warfare. Effectively we now have an Offensive Biological Warfare Industry in this country that violates theBiological Weapons Conventionand myBiological Weapons Anti-Terrorism Act of 1989.

The law Boyle drafted states: "Whoever knowingly develops, produces, stockpiles, transfers, acquires, retains, or possesses any biological agent, toxin, or delivery system for use as a weapon, or knowingly assists a foreign state or any organization to do so, shall be fined under this title or imprisoned for life or any term of years, or both. There is extraterritorial Federal jurisdiction over an offense under this section committed by or against a national of the United States."

Boyle also warned:

Russia and China have undoubtedly reached the same conclusions I have derived from the same open and public sources, and have responded in kind. So what the world now witnesses is an all-out offensive biological warfare arms race among the major military powers of the world: United States, Russia, Britain, France, China, Israel, inter alia.

We have reconstructed the Offensive Biological Warfare Industry that we had deployed in this county before its prohibition by the Biological Weapons Convention of 1972, described by Seymour Hersh in his groundbreaking expose "Chemical and Biological Warfare: America's Hidden Arsenal." (1968)

Boyle now states that he has been "blackballed" in the media on this issue, despite his having written the relevant statute. The group he worked with on the law, the Council for Responsible Genetics, went under several years ago, making Boyle's views against "biodefense" even more marginal as government money for dual use work poured into the field and criticswithin the scientific community have fallen silent. In turn, his denunciationshave grown more sweeping.

In the 1990 book "Preventing a Biological Arms Race," scholar Susan Wright argued that current laws regarding bioweapons were insufficient, as there were "projects in which offensive and defensive aspects can be distinguished only by claimed motive." Boyle notes, correctly, that current law he drafted does not makean exception for "defensive" work, but only for "prophylactic, protective or other peaceful purposes."

While Boyle is particularly vociferous in his condemnations, he is not alone. There has been irregular, but occasional media attention to this threat. The Guardian ran a piece in 2014,"Scientists condemn 'crazy, dangerous' creation of deadly airborne flu virus," afterKawaoka created a life-threatening virus that "closely resembles the 1918 Spanish flu strain that killed an estimated 50m people":

"The work they are doing is absolutely crazy. The whole thing is exceedingly dangerous," said Lord May, the former president of the Royal Society and one time chief science adviser to the UK government. "Yes, there is a danger, but it's not arising from the viruses out there in the animals, it's arising from the labs of grossly ambitious people."

Boyle'scharges beginning early this yearthat the coronavirus was bioengineered allegationsrecently mirrored by French virologist andNobel laureate Luc Montagnier have not been corroborated by any publicly produced findings of any U.S. scientist. Boyle even charges that scientists like Ebright, who is at Rutgers, arecompromised because the university got abiosafety level 3 lab in 2017though Ebright is perhaps the most vocal eminent critic of this research, among U.S. scientists. These and other controversies aside, Boyle's concerns about the dangers of biowarfare arelegitimate; indeed, Ebright shares them.

Some of the most vocal voices to discuss the origins of the novel coronavirushave been eager to minimizethe dangers of lab work, or have focused almost exclusively on "wet markets" or "exotic" animals as the likely cause.

The media celebrated Laurie Garrett, the Pulitzer Prizewinning author and former senior fellow at the Council on Foreign Relations, when she declared on Twitter on March 3 (in a since-deleted tweet)that the origin of the pandemic was discovered: "It's pangolins. #COVID19 Researchers studied lung tissue from 12 of the scaled mammals that were illegally trafficked in Asia and found #SARSCoV2 in 3. The animals were found in Guangxi, China. Another virus+ smuggled sample found in Guangzhou."

She was swiftly corrected by Ebright: "Arrant nonsense. Did you even read the paper? Reported pangolin coronavirus is not SARS-CoV-2 and is not even particularly close to SARS-CoV-2. Bat coronavirus RaTG13 is much closer to SARS-CoV-2 (96.2% identical) than reported pangolin coronavirus (92.4% identical)." He added: "No reason to invoke pangolin as intermediate. When A is much closer than B to C, in the absence of additional data, there is no rational basis to favor pathway A>B>C over pathway A>C." When someone asked what Garrett was saying, Ebright responded: "She is saying she is scientifically illiterate."

The following day, Garrett corrected herself (without acknowledging Ebright): "I blew it on the #Pangolins paper, & then took a few hours break from Twitter. It did NOT prove the species = source of #SARSCoV2. There's a torrent of critique now, deservedly denouncing me & my posting. A lot of the critique is super-informative so leaving it all up 4 while."

At leastone Chinese governmentofficialhas respondedto the allegation that the labs in Wuhan could be the source for the pandemic by alleging that perhaps the U.S. isresponsibleinstead. In American mainstreammedia, that has been reflexivelytreated as evenmore ridiculousthan the original allegation that the virus could havecome froma lab.

Obviouslythe Chinese government'sallegations should not be taken at face value, but neither should U.S. government claims especially considering that U.S. government labs were the apparent source for theanthrax attacks in 2001. Those attacks sent panic through the U.S. and shut down Congress, allowing the Bushadministration to enact the PATRIOT Act and ramp up the invasions of Afghanistan and Iraq. Indeed, in October2001, media darlings like Richard Butler and Andrew Sullivan propagandizedfor war with Iraq because of the anthrax attacks. (Neither Iraq nor al-Qaida was involved.)

The 2001 anthrax attacks also provided muchof the pretext forthe surge in biolab spending since then, even though they apparently originated in a U.S. or U.S.-allied lab. Indeed, thoseattacks remain shrouded in mystery.

The U.S. government has also come up withelaborate cover stories to distract from its bioweapons work. For instance, the U.S. government infamously claimed the 1953 death of Frank Olson, a scientist at Fort Detrick, Maryland, was anLSD experiment gone wrong;it now appears to have been an execution to cover up for U.S.biological warfare.

Regardless of the cause of the current pandemic, these biowarfare/biodefense labs need far more scrutiny. The call to shut them down by Boyle and others needs to be clearly heard and light must be shone on precisely what research is being conducted.

The secrecy of these labs may prevent us ever knowing with certainty the origins of the current pandemic.What we do know is this kind of lab work comes with real dangers. One might make a comparison to climate change: We cannot attribute an individual hurricane to man-made climate disruption,yet science tells us that human activity makes stronger hurricanes more likely. Thatbrings us back to the imperative to cease the kinds of activities thatproduce such dangers in the first place.

If that doesn't happen, the people of the planet will be at the mercy of the machinations and mistakes of state actors who are playing with fire for their geopolitical interests.

View original post here:
Did this virus come from a lab? Maybe not but it exposes the threat of a biowarfare arms race - Salon

As the coronavirus pandemic continues unabated around the world, we are, understandably, all concerned about the best ways to protect ourselves against viruses and other infections.

First and foremost, we all need to follow government advice to stay home and social distance. But, beyond this, we can all use the time to rest up and dose up so that when we are able to get back to work, we are geared up to stay healthy and thrive.

I consider myself a natural biohacking expert. Biohacking is the practice of enhancing our bodies and our health through science and self-experimentation. It can be as simple as implementing lifestyle and dietary changes that improve the functioning of your body, or as extreme as using implant technology and genetic engineering. I believe in the power of food, utilising the natural chemistry of the body and good cognitive function to slow the ageing process, strengthen our immune systems and generally make us superhuman.

Incorporating some of these simple biohacks into your routine is the most effective way to ensure your defences are as effective as they can be against viral infection and pathogens.

You are what you eat (and put anywhere near your body)

We are, quite literally, what we eat. We live in a symbiotic relationship with around 30 trillion microbes that live in our bodies, collectively making up our microbiome. Our microbiome programmes our immune system and is strengthened by fermented foods, fibre, pulses and plant-based food in general. Make sure you eat as balanced a diet as possible. Otherwise, you are just leaving the door open for enemy viruses to walk straight in and start making themselves at home. Superfoods that feature in my diet everyday include bee pollen (an antioxidant that speeds up healing) aai (contains healthy fats and could be anti-cancer agent) and blue spirulina (improves muscles strength and endurance).

Use supplements strategically

I use a range of supplements to complement my diet and ensure I am giving my body the nutrients it needs to stay healthy. The combination you take will depend on your age, gender, whether youre pregnant and even where you live. Vitamin D is advised for most people, particularly as it can be difficult to get enough through your diet alone. These nutrients are needed to keep bones, teeth and muscles healthy. Echinacea is one of the most popular immune-boosting herbs, it can reduce inflammation and has been found to shorten the duration of flu-like viruses. I also take vitamin C, zinc and probiotic supplements.

Stay active- but rest is just as important

To enjoy a functioning immune system it will come as no surprise that exercise is key, but the impact that sleep has on our bodies is less well known. In our industry, were used to a work hard, play hard culture, but if were not getting enough sleep then were putting ourselves at risk of burning out and succumbing to illness. Long-term, a lack of sleep can increase the risk of conditions such as heart disease, diabetes and obesity. Sleep is your bodys time to repair and reset- and it will switch off your bodys chemical stress response too.

The current public health emergency has given us all time to pause and reflect. If youre lucky enough to be able to stay home and stay safe, why not try to incorporate some of these natural bio hacks into your life? Youll feel the benefits in no time.s

Continue reading here:
Comment: Nassau executive chef Silvena Rowe on biohacking the body - Caterer Middle East

Scientists at the University of California-San Diego say they have moved one step closer to the ability to make heparin in cultured cells. Heparin is a potent anti-coagulant and the most prescribed drug in hospitals, yet cell-culture-based production of heparin is currently not possible, according to the researchers who published their study, ZNF263 is a transcriptional regulator of heparin and heparan sulfate biosynthesis in PNAS.

In particular, the researchers found a critical gene in heparin biosynthesis: ZNF263 (zinc-finger protein 263). The team believes this gene regulator is a key discovery on the way to industrial heparin production. The idea would be to control this regulator in industrial cell lines using genetic engineering, paving the way for safe industrial production of heparin in well-controlled cell culture.

Heparin is the most widely prescribed biopharmaceutical in production globally. Its potent anticoagulant activity and safety makes it the drug of choice for preventing deep vein thrombosis and pulmonary embolism. In 2008, adulterated material was introduced into the heparin supply chain, resulting in several hundred deaths and demonstrating the need for alternate sources of heparin. Heparin is a fractionated form of heparan sulfate derived from animal sources, predominantly from connective tissue mast cells in pig mucosa. While the enzymes involved in heparin biosynthesis are identical to those for heparan sulfate, the factors regulating these enzymes are not understood, write the investigators.

Examination of the promoter regions of all genes involved in heparin/heparan sulfate assembly uncovered a transcription factor-binding motif for ZNF263, a C2H2 zinc finger protein. CRISPR-mediated targeting and siRNA knockdown of ZNF263 in mammalian cell lines and human primary cells led to dramatically increased expression levels of HS3ST1, a key enzyme involved in imparting anticoagulant activity to heparin, and HS3ST3A1, another glucosaminyl 3-O-sulfotransferase expressed in cells. Enhanced 3-O-sulfation increased binding to antithrombin, which enhanced Factor Xa inhibition, and binding of neuropilin-1. Analysis of transcriptomics data showed distinctively low expression of ZNF263 in mast cells compared with other (nonheparin-producing) immune cells. These findings demonstrate a novel regulatory factor in heparan sulfate modification that could further advance the possibility of bioengineering anticoagulant heparin in cultured cells.

The UC San Diego scientists reasoned that heparin synthesis must be under the control of transcription factors, whose tissue-specific occurrence might give mast cells the unique ability to produce heparin. Since regulators for heparin were not known, a research team led by UC San Diego professors Jeffrey Esko, PhD, and Nathan Lewis, PhD, used bioinformatic software to scan the genes encoding enzymes involved in heparin production and specifically look for sequence elements that could represent binding sites for transcription factors. The existence of such a binding site could indicate that the respective gene is regulated by a corresponding gene regulator protein, i.e. a transcription factor.

One DNA sequence that stood out the most is preferred by a transcription factor called ZNF263 (zinc-finger protein 263), explains Lewis, who holds appointments in the UC San Diego School of Medicines Department of Pediatrics and in the UC San Diego Jacobs School of Engineerings Department of Bioengineering.

Using CRISPR/Cas9, the researchers mutated ZNF263 in a human cell line that normally does not produce heparin. They found that the heparan sulfate that this cell line would normally produce was now chemically altered and showed a reactivity that was closer to heparin. Experiments further showed that ZNF263 represses key genes involved in heparin production. Analysis of gene expression data from human white blood cells showed suppression of ZNF263 in mast cells (which produce heparin in vivo) and basophils, which are related to mast cells. The researchers report that ZNF263 appears to be an active repressor of heparin biosynthesis throughout most cell types, and mast cells are enabled to produce heparin because ZNF263 is suppressed in these cells.

This finding could have important relevance in biotechnology. Cell lines used in industry (such as CHO cells that normally are unable to produce heparin) could be genetically modified to inactivate ZNF263 which could enable them to produce heparin, like mast cells do.

Philipp Spahn, PhD, a project scientist in the Lewis lab, described further directions the team is pursuing: Our bioinformatic analysis revealed several additional potential gene regulators which can also contribute to heparin production and are now exciting objects of further study.

Visit link:
Researchers Move Closer to Industrial Production of Heparin in Cell Culture - Genetic Engineering & Biotechnology News

Share this Article

You are free to share this article under the Attribution 4.0 International license.

A new model aims to predict genetic changes that have unintended consequences in trees that researchers genetically modify.

It could pave the way for more efficient research in the fields of both genetic modification and forestry.

Researchers want to genetically modify trees for a variety of applications, from biofuels to paper production. They also want to steer clear of modifications to one gene that result in unexpected changes to other genes.

The research at issue focuses on lignin, a complex material found in trees that helps to give trees their structure. It is, in effect, what makes wood feel like wood.

Whether you want to use wood as a biofuel source or to create pulp and paper products, there is a desire to modify the chemical structure of lignin by manipulating lignin-specific genes, resulting in lignin that is easier to break down, says corresponding author Cranos Williams, an associate professor of electrical and computer engineering at North Carolina State University. However, you dont want to make changes to a trees genome that compromise its ability to grow or thrive.

The researchers focused on a tree called Populus trichocarpa, which is a widely used model organismmeaning that scientists who study genetics and tree biology spend a lot of time studying P. trichocarpa.

Previous research generated models that predict how independent changes to the expression of lignin genes impacted lignin characteristics, says Megan Matthews, first author of the paper, a former PhD student at NC State, and a current postdoctoral researcher at the University of Illinois.

These models, however, do not account for cross-regulatory influences between the genes. So, when we modify a targeted gene, the existing models do not accurately predict the changes we see in how non-targeted genes are being expressed. Not capturing these changes in expression of non-targeted genes hinders our ability to develop accurate gene-modification strategies, increasing the possibility of unintended outcomes in lignin and wood traits.

To address this challenge, we developed a model that was able to predict the direct and indirect changes across all of the lignin genes, capturing the effects of multiple types of regulation. This allows us to predict how the expression of the non-targeted genes is impacted, as well as the expression of the targeted genes, Matthews says.

Another of the key merits of this work, versus other models of gene regulation, is that previous models only looked at how the RNA is impacted when genes are modified, Matthews says. Those models assume the proteins will be impacted in the same way, but thats not always the case. Our model is able to capture some of the changes to proteins that arent seen in the RNA, or vice versa.

This model could be incorporated into larger, multi-scale models, providing a computational tool for exploring new approaches to genetically modifying tree species to improve lignin traits for use in a variety of industry sectors.

In other words, by changing one gene, researchers can accidentally mess things up with other genes, creating trees that arent what they want. The new model can help researchers figure out how to avoid that.

The paper appears in the journal PLOS Computational Biology. Support for the work came from the National Science Foundation and a National Physical Science Consortium Graduate Fellowship.

Source: NC State

View post:
Model warns of genetic modification gone awry in trees - Futurity: Research News

Researchers are interested in genetically modifying trees for a variety of applications, from biofuels to paper production. They also want to steer clear of modifications with unintended consequences. These consequences can arise when intended modifications to one gene results in unexpected changes to other genes. A new model aims to predict these changes, helping to avoid unintended consequences, and hopefully paving the way for more efficient research in the fields of genetic modification and forestry.

The research at issue focuses on lignin, a complex material found in trees that helps to give trees their structure. It is, in effect, what makes wood feel like wood.

Whether you want to use wood as a biofuel source or to create pulp and paper products, there is a desire to modify the chemical structure of lignin by manipulating lignin-specific genes, resulting in lignin that is easier to break down, says Cranos Williams, corresponding author of a paper on the work and an associate professor of electrical and computer engineering at NCState. However, you dont want to make changes to a trees genome that compromise its ability to grow or thrive.

The researchers focused on a tree called Populus trichocarpa, which is a widely used model organism meaning that scientists who study genetics and tree biology spend a lot of time studying P. trichocarpa.

Previous research generated models that predict how independent changes to the expression of lignin genes impacted lignin characteristics, says Megan Matthews, first author of the paper, a former Ph.D. student at NCState and a current postdoc at the University of Illinois. These models, however, do not account for cross-regulatory influences between the genes. So, when we modify a targeted gene, the existing models do not accurately predict the changes we see in how non-targeted genes are being expressed. Not capturing these changes in expression of non-targeted genes hinders our ability to develop accurate gene-modification strategies, increasing the possibility of unintended outcomes in lignin and wood traits.

To address this challenge, we developed a model that was able to predict the direct and indirect changes across all of the lignin genes, capturing the effects of multiple types of regulation. This allows us to predict how the expression of the non-targeted genes is impacted, as well as the expression of the targeted genes, Matthews says.

Another of the key merits of this work, versus other models of gene regulation, is that previous models only looked at how the RNA is impacted when genes are modified, Matthews says. Those models assume the proteins will be impacted in the same way, but thats not always the case. Our model is able to capture some of the changes to proteins that arent seen in the RNA, or vice versa.

This model could be incorporated into larger, multi-scale models, providing a computational tool for exploring new approaches to genetically modifying tree species to improve lignin traits for use in a variety of industry sectors.

In other words, by changing one gene, researchers can accidentally mess things up with other genes, creating trees that arent what they want. The new model can help researchers figure out how to avoid that.

The paper, Modeling cross-regulatory influences on monolignol transcripts and proteins under single and combinatorial gene knockdowns in Populus trichocarpa, is published in the journal PLOS Computational Biology. The paper was co-authored by Ronald Sederoff, a professor emeritus of forestry and environmental resources at NCState; Jack Wang, an assistant professor of forestry and environmental resources at NCState; and Vincent Chiang, a Jordan Family Distinguished Professor Emeritus and Alumni Outstanding Research Professor with the Forest Biotechnology Group at NCState.

This work was supported by the National Science Foundation Grant DBI-0922391 to Chiang and by a National Physical Science Consortium Graduate Fellowship to Matthews.

-shipman-

Note to Editors: The study abstract follows.

Modeling cross-regulatory influences on monolignol transcripts and proteins under single and combinatorial gene knockdowns in Populus trichocarpa

Authors: Megan L. Matthews, Ronald Sederoff and Cranos M. Williams, North Carolina State University; Jack P. Wang and Vincent L. Chiang, Northeast Forestry University, Harbin, China, and North Carolina State University

Published: April 10, PLOS Computational Biology

Abstract: Accurate manipulation of metabolites in monolignol biosynthesis is a key step for controlling lignin content, structure, and other wood properties important to the bioenergy and biomaterial industries. A crucial component of this strategy is predicting how single and combinatorial knockdowns of monolignol specific gene transcripts influence the abundance of monolignol proteins, which are the driving mechanisms of monolignol biosynthesis. Computational models have been developed to estimate protein abundances from transcript perturbations of monolignol specific genes. The accuracy of these models, however, is hindered by their inability to capture indirect regulatory influences on other pathway genes. Here, we examine the manifestation of these indirect influences on transgenic transcript and protein abundances, identifying putative indirect regulatory influences that occur when one or more specific monolignol pathway genes are perturbed. We created a computational model using sparse maximum likelihood to estimate the resulting monolignol transcript and protein abundances in transgenicPopulus trichocarpabased on targeted knockdowns of specific monolignol genes. Using in-silicosimulations of this model and root mean square error, we showed that our model more accurately estimated transcript and protein abundances, in comparison to previous models, when individual and families of monolignol genes were perturbed. We leveraged insight from the inferred network structure obtained from our model to identify potential genes, including PtrHCT, PtrCAD, and Ptr4CL, involved in post-transcriptional and/or post-translational regulation. Our model provides a useful computational tool for exploring the cascaded impact of single and combinatorial modifications of monolignol specific genes on lignin and other wood properties.

Continue reading here:
Better Predicting the Unpredictable Byproducts of Genetic Modification - NC State News

University Relations

Sarah DuRant and Jeffrey Lewis, assistant professors of biology, were awarded major early career awards by the National Science Foundation.

FAYETTEVILLE, Ark. Two researchers Sarah DuRant and Jeffrey Lewis from the Department of Biological Sciences in the J. William Fulbright College of Arts and Sciences recently received Faculty Early Career Development Awards from the National Science Foundation. DuRant, an assistant professor, received $1.5 million, while Lewis, also an assistant professor, received $1.2 million.

Known as CAREER awards, they are the NSF's most prestigious award for early-career faculty who have the potential to serve as academic role models in research and education and to lead advances in the mission of their department or organization. The awards are for five years and include teaching and public-outreach components.

Working with domestic canaries, DuRant plans to study the effects of disease on avian parental care behaviors and subsequent offspring responses to disease, including likelihood of disease transmission.

"In the world of the disease, a lot of focus is on how mothers, when they are exposed to a pathogen, develop antibodies to the pathogen and can pass them along to the offspring," she said. "One of the things I am interested in how behavior is shaping the immune phenotype of the offspring."

A pathogen can affect reproductive traits in parents such as incubation behaviors, DuRant explained, which in turn shape how an offspring responds to pathogens. "Ultimately what can happen is that how any individual responds to the pathogen can start to shape pathogen growth, transmission and virulence."

Lewis is studying how organisms with different genetic makeups respond differently to environmental stress. Using brewer's yeast, he will try to unlock the reasons why some strains are more sensitive to high levels of stresses such as ethanol than others.

"In pretty much every organism, if you expose them to mild stress there are a bunch of stress-protective proteins that get turned on," he said. "The thought has long been that this response is for adapting to that initial stress. But the genes getting turned on by stress seemed largely dispensable for stress survival. The big question was why is the cell turning these genes on if they are not required to protect cell from insult that provoked the response?"

It turns out that the function of the proteins is, in part, to protect the cell against future severe stress, "analogous to vaccinating the cell," he said.

Yeast cells are easy to grow and manipulate with genetic engineering, he added, making them a good test subject for identifying the genes necessary for acquiring resistance to severe stress. "We can grow billions of them really easily and do high-throughput genetics really easily."

A side benefit is that the research could lead to improved yeast strains for brewing beer. "Some strains do better withstanding brewing stresses than others. We will have students analyze and incorporate genomic data and gain experience with that."

Both DuRant and Lewis are in the first year of the five-year CAREER funding cycle.

See the article here:
University of Arkansas Biologists Receive NSF CAREER Awards - University of Arkansas Newswire

One of the major limitations of the first-generation rDNA-based GM methods is the randomness of DNA insertions into plant genomes, just as the earlier mutagenesis methods introduced mutations randomly. The newer methods increase the specificity and precision with which genetic changes can be made. Known under the general rubric of sequence-specific nuclease (SSN) technology or gene/genome-editing, this approach uses proteins or protein-nucleic acid complexes that bind to and cut specific DNA sequences.1 SSNs include transcription activator-like effector nucleases (TALENs), zinc-finger nucleases (ZFNs), and meganucleases.2

[This is part three of a four-part series on the progress of agricultural biotechnology. Read part one and part two.]

The DNA cuts made by SSNs are repaired by cellular processes that often either change one to several base pairs or introduce deletions and/or insertions (aka indels) at the target site. Another recently added technology capable of editing gene sequences is termed oligonucleotide-directed mutagenesis (ODM) and uses short nucleic acid sequences to target mutations to selected sites.3

The hottest and the coolest

What is rapidly emerging as the most powerful of the SSN technologies is known by the uninformative acronym CRISPR/Cas, which contracts the unwieldy designation clustered regularly interspaced short palindromic repeats (CRISPR)CRISPR-associated protein (Cas9). Its based on a bacterial defense system against invading viruses and promises extraordinary versatility in the kinds of genome changes that it can make.1,4

The CRISPR/Cas editing molecular machine is comprised of an enzyme (Cas9 and other variants) that binds an RNA molecule (called the guide RNA or gRNA) whose sequence guides the complex to the matching genomic sequence, allowing the Cas9 enzyme to introduce a double-strand break within the matching sequence. The CRISPR/Cas system can be used to edit gene sequences, to introduce a gene or genes at a pre-identified site in the genome, and to edit multiple genes simultaneously, none of which could be done with rDNA methods.1,5

Many of the genetic changes created using either SSN or ODM are indistinguishable at the molecular level from those that occur in nature or are produced by mutation breeding. Since both spontaneous mutants and chemical- and radiation-induced mutants have been used in crop improvement without regulation, there is no scientific rationale for regulating mutants produced by the newer methods. In hopes of creating a distinction that will permit exemption of gene-edited crops from regulation, the newer methods are increasingly referred to as new plant breeding techniques (NPBTs or just NBTs).

Quick successes for NBTs?

Prime targets of gene editing are cellular proteins that are involved in pathogenesis.6 Virus reproduction requires the recruitment of cellular proteins for replication, transcription and translation. There can be sufficient redundancy in the requisite protein infrastructure so that partial or complete virus resistance can be achieved by disrupting genes that code for proteins required for viral replication without damaging crop productivity.

For example, work with mutants of the model plant Arabidopsis identified translation initiation factor eIF4E as required for potyvirus translation. CRISPR/Cas-induced point mutations and deletions have recently been reported to enhance viral resistance not only in Arabidopsis, but in cucumber and cassava, as well.7

The many ways that plants and their bacterial and fungal pathogens interact offer opportunities to use gene editing to enhance plant disease resistance and reduce agricultures dependence on chemical control agents.6 The two main strategies are to inactivate genes whose products render the host plant sensitive to pathogen invasion and to enhance the ability of the host plant to resist invasion by providing functional resistance factors they lack.

An example of the former is provided by the mildew resistance resulting from the inactivation of all three homeoalleles of the mildew resistance locus (MLO) of hexaploid wheat.8 The efficiency of targeting both multiple alleles and multiple loci has taken a further jump with the development of multiplexed gene editing using vectors carrying several gRNA sequences capable of being processed by cellular enzymes to release all of them. This allows the gRNAs to edit multiple genes simultaneously.9

The second approach is to capitalize on the formidable arsenal of resistance genes residing in plant genomes.10 Fungal resistance genes have long been a major target of breeders efforts and have proved frustratingly short-lived, as pathogens rapidly evolve to evade recognition.11 While desirable resistance genes missing from domesticated crops still reside in wild relatives, extracting them by conventional breeding methods can be time-consuming or impossible.

European academic researchers created transgenic potatoes resistant to the late blight (Phytophthora infestans) that caused the Irish potato famine by inserting resistance (R) genes cloned from wild potato species into commercial potato varieties.12 A blight-resistant variety, called the Innate Generation 2 potato, is being commercialized by J.R. Simplot company in the U.S. and Canada and is already being marketed in the U.S. as the White Russet Idaho potato.13 Transgenic disease-resistance traits have been introduced in other crops, but have yet to be commercialized.14

Plant genomes contain hundreds to thousands of potential R genes, but it is not yet possible to determine whether a given one will confer resistance to a particular pathogen. Methods are currently being developed to accelerate the identification and cloning of active ones.14 Once identified, CRISPR/Cas can be used to introduce cassettes carrying multiple R genes, making it possible to create more durable resistance than can be achieved by introducing a single R gene through conventional breeding14. Finally, direct editing of resident inactive R genes using a ribonucleoprotein (RNP) strategy that avoids creating a transgenic plant may prove useful, although no such products appear to be in the pipeline to commercialization at present.15,16

Multiplexed editing has proved particularly useful for editing genes in polyploid species. For example, Cas9/sgRNA-mediated knockouts of the six fatty acid desaturase 2 (FAD2) genes of allohexaploid Camelina sativa was reported to markedly improve the fatty acid composition of Camelina oil.17 Using a different approach, Yield10 Biosciences is moving toward commercialization of a high-oil Camelina developed by editing a negative regulator of acetyl-CoA carboxylase.18

As of this writing, the only gene-edited product that has been commercialized is a soybean oil with no trans-fat, trademarked Calyno, developed by Calyxt.19 Gene-edited crops that have been approved but not commercialized or are still in the regulatory pipeline include miniature tomatoes, high-fiber wheat, high-yield tomatoes, improved quality alfalfa, non-browning potatoes and mushrooms, as well as high starch-content and drought-resistant corn, most being developed by small biotech companies.19

Getting beyond the low-hanging fruit

It is becoming increasingly clear that yield increases in our major crops by traditional breeding approaches are not keeping pace with demand.20 The gap is likely to widen as climate warming moves global temperatures farther from those prevailing when our crops were domesticated.

Overexpression of stress-related transcription factors has been reported to increase yields under water-stress conditions, but such increases are generally not maintained under optimal conditions.21 Monsantos drought-tolerant (Genuity DroughtGard) corn hybrids are based on the introduction of bacterial chaperone genes.22 Fortunately, research into drought stress tolerance in wheat and other grains continues apace, although no drought-tolerant varieties have yet reached farmers.23

Real progress on crop yield is slow. What stands in the way is that we have so limited an understanding of how plants work at the molecular level. At every level of analysis, organisms are redundant networks of interconnected proteins that adjust their manifold physical and enzymatic interactions in response to internal signals and external stimuli, then send messages to the information storage facilities (DNA) to regulate their own production and destruction rates.

As well, many genes are present in families of between two and hundreds or thousands of similar members, making it difficult to determine either the function or the contribution of any given member to a complex trait such as stress tolerance or yield. That said, gene family functions are identifiable and some, such as transcription factor genes, encode proteins that influence multiple other genes, making them among the likeliest candidates for manipulation. Indeed, studies on the genetics of domestication often point to changes in transcription factor genes.24

But while there have been reports that constitutive overexpression of single transcription factor gene can increase grain yield in both wheat and maize, none appear to have been commercialized yet.25 The challenge of developing a yield-improved variety by simply overexpressing transcription factor genes is illustrated by a recent report from Corteva.26 It describes a tour-de-force involving generation and testing of countless transgenic plants to identify a single transcription factor gene, ZMM28, that reproducibly increased yield when incorporated into 48 different hybrids and tested over a 4-year period in 58 locations.26

Getting there by a different route

Might gene-editing facilitate the task of generating and identifying yield-enhancing genetic variation? While the CRISPR/Cas toolkit is growing at dizzying speed, its utility in crop improvement has so far been limited to the simple traits controlled by individual genes, albeit including multiple alleles.1,27

Crop domestication and plant breeding have vastly narrowed genetic diversity because the very process of selecting plants with enhanced traits imposes a bottleneck, assuring that only a fraction of the ancestral populations genetic diversity is represented in a new elite variety. This, in turn, limits what can be done by mutagenizing existing elite varieties, a process that is also burdened with the necessity to eliminate deleterious mutations through back-crossing.

But to widen the genetic base and to modify genes that contribute to quantitative traits, it is still first necessary to identify the genes that contribute to agronomically important traits. Identifying such genes is currently a slow and tedious process of conventional and molecular mapping.28 A recent report describes a method for combining pedigree analysis with targeted CRISPR/Cas-mediated knockouts that promises to markedly accelerate the identification of the individual contributing genes in the chromosomal regions that are associated with quantitative traits, technically known as quantitative trait loci (QTLs).29

Even as the QTL knowledge gap narrows, gRNA multiplexing is extending the power of SSNs to understanding and modifying complex traits in crop plants. For example, using multiplexed gRNAs, Cas nuclease was simultaneously targeted to three genes known to be negative regulators of grain weight in rice.30 The triple mutants were reported to exhibit increases in the neighborhood of 25% in each of the three grain weight traits: length, width and thousand grain weight.

In another study, 8 different genes affecting rice agronomic traits were targeted with a single multiplexed gRNA construct and all showed high mutation efficiencies in the first generation.31 Conversely, it has been reported that editing the same QTLs gives different outcomes in different elite varieties, improving yield in some but not other.32

Mutations affecting the expression of regulatory genes, such as transcription factors genes, account for a substantial fraction of the causative genetic changes during crop domestication.33 Multiplexed gRNAs constructs targeting cis-regulatory elements (CREs) have been used to generate large numbers of allelic variants of genes affecting fruit size in tomato, mimicking some of the mutations accumulated during domestication and breeding of contemporary tomato varieties.34

Knowledge of domestication genes can also be used to accelerate domestication of wild plants that retain traits of value, such as salt tolerance, as reported for tomato.35 This opens the possibility of rapidly domesticating wild species better adapted to the harsher climate conditions of the future.

While the above-described advances have been based on the CRISPR/Cas-mediated deletions, approaches to more precise sequence editing are developing as well. While Cas-generated cuts in the DNA are most commonly repaired by the non-homologous end joining pathway (NHEJ), the less frequent homology-directed repair pathway (HDR) has been shown to edit sequences at useful frequencies using Cas-gRNA ribonucleoprotein complexes.15,36

As well, mutant Cas9 proteins lacking nuclease activity have been fused with base-editing enzymes such as cytidine and adenosine deaminases to direct gene editing without DNA cleavage.37,38 This approach can change single base pairs precisely in both coding and non-coding regions, as well alter mRNA precursor processing sites.38 Finally, the sequence targeting properties of the CRISPR-Cas system can be used to deliver other types of hybrid proteins to target sequences to regulate gene expression and DNA methylation.27

In sum, the many variations on gene editing now developing hold the promise of revolutionizing crop breeding, prompting several colleagues to whimsically title a recent review of CRISPR/Cas-based methodology: Plant breeding at the speed of light.39 And indeed, the new methods make it possible to replace chemicals with biological mechanisms in protecting plants from pests and disease, as well as increase their resilience to stress.

That said, extraordinary progress in increasing grain yields has already been accomplished by what are now considered to be traditional breeding methods and increased fertilizer use. Further improvements continue, but will likely be harder won than the many-fold increases in corn, wheat and rice yields of the last century and its Green Revolution. But there is a persistent disconnect between what can be done to accelerate plant breeding using the new gene-editing toolkit and what is actually being done by both the public and private sectors to get varieties improved by these methods out to farmers.

1Zhang Y et al. (2019). The emerging and uncultivated potential of CRISPR technology in plant science. Nature Plants 5:778-94.

2Podevin N et al. (2013). Site-directed nucleases: a paradigm shift in predictable, knowledge-based plant breeding. Trends Biotechnol 31:375-83.

3Sauer NJ et al. (2016). Oligonucleotidedirected mutagenesis for precision gene editing. Plant Biotechnol J 14:496-502.

4Zhang D et al. (2016). Targeted gene manipulation in plants using the CRISPR/Cas technology. J Genet Genomics 43:251-62.

5Cong L et al. (2013). Multiplex genome engineering using CRISPR/Cas systems. Science 339:819-23.

6Borrelli VM et al. (2018). The enhancement of plant disease resistance using CRISPR/Cas9 technology. Frontiers Plant Sci 9:Article 1245.

7Chandrasekaran J et al. (2016). Development of broad virus resistance in nontransgenic cucumber using CRISPR/Cas9 technology. Molec Plant Pathol 17:1140-53; Pyott DE et al. (2016). Engineering of CRISPR/Cas9mediated potyvirus resistance in transgenefree Arabidopsis plants. Molec Plant Pathol 17:1276-88; Gomez MA et al. (2019). Simultaneous CRISPR/Cas9mediated editing of cassava eIF 4E isoforms nCBP1 and nCBP2 reduces cassava brown streak disease symptom severity and incidence. Plant Biotechnol J 17:421-34.

8Wang Y et al. (2014). Simultaneous editing of three homoeoalleles in hexaploid bread wheat confers heritable resistance to powdery mildew. Nature Biotechnol 32:947.

9Xie K et al. (2015). Boosting CRISPR/Cas9 multiplex editing capability with the endogenous tRNA-processing system. Proc Natl Acad Sci 112:3570-5; Wang W et al. (2018). Transgenerational CRISPR-Cas9 activity facilitates multiplex gene editing in allopolyploid wheat. The CRISPR J 1:65-74.

10Petit-Houdenot Y and Fudal I (2017). Complex interactions between fungal avirulence genes and their corresponding plant resistance genes and consequences for disease resistance management. Frontiers Plant Sci 8:1072.

11Bebber DP and Gurr S (2015). Crop-destroying fungal and oomycete pathogens challenge food security. Fungal Genet Biol 74:62-4; van Esse HP et al. (2020). Genetic modification to improve disease resistance in crops. New Phytol 225:70-86.

12Jones JD et al. (2014). Elevating crop disease resistance with cloned genes. Phil Trans Royal Soc B: Biol Sci 369:20130087; Haesaert G et al. (2015). Transformation of the potato variety Desiree with single or multiple resistance genes increases resistance to late blight under field conditions. Crop Protection 77:163-75.

13Halsall M. Innate outlook. Spudsmart, 24 April 2019 https://spudsmart.com/innate-outlook/

14Dong OX and Ronald PC (2019). Genetic engineering for disease resistance in plants: recent progress and future perspectives. Plant Physiol 180:26-38.

15Svitashev S et al. (2016). Genome editing in maize directed by CRISPRCas9 ribonucleoprotein complexes. Nature Communications 7:1-7.

16Mao Y et al. (2019). Gene editing in plants: progress and challenges. Nat Sci Rev 6:421-37.

17Morineau C et al. (2017). Selective gene dosage by CRISPRCas9 genome editing in hexaploid Camelina sativa. Plant Biotechnol J 15:729-39; Jiang WZ et al. (2017). Significant enhancement of fatty acid composition in seeds of the allohexaploid, Camelina sativa, using CRISPR/Cas9 gene editing. Plant Biotechnol J 15:648-57.

18Yield10 Bioscience (Jan 16, 2020 ). Yield10 Bioscience submits Am I Regulated? letter to USDA-APHIS BRS for CRISPR genome-edited C3007 in Camelina to pave the way for U.S. field tests. https://www.globenewswire.com/news-release/2020/01/16/1971418/0/en/Yield10-Bioscience-Submits-Am-I-Regulated-Letter-to-USDA-APHIS-BRS-for-CRISPR-Genome-Edited-C3007-in-Camelina-to-Pave-the-Way-for-U-S-Field-Tests.html

19Genetic Literacy Project (2020). Global Gene Editing Regulation Tracker. https://crispr-gene-editing-regs-tracker.geneticliteracyproject.org/united-states-crops-food/

20Ray DK et al. (2013). Yield trends are insufficient to double global crop production by 2050. PloS One 8:e66428.

21Rice EA et al. (2014). Expression of a truncated ATHB17 protein in maize increases ear weight at silking. PLoS One 9:e94238; Araus JL et al. (2019). Transgenic solutions to increase yield and stability in wheat: shining hope or flash in the pan? J Experimental Bot 70:1419-24.

22Castiglioni P et al. (2008). Bacterial RNA chaperones confer abiotic stress tolerance in plants and improved grain yield in maize under water-limited conditions. Plant Physiol 147:446-55.

23Mwadzingeni L et al. (2016). Breeding wheat for drought tolerance: Progress and technologies. J Integrative Agricult 15:935-43; Sallam A et al. (2019). Drought stress tolerance in wheat and barley: Advances in physiology, breeding and genetics research. Internat J Mol Sci 20:3137.

24Swinnen G et al. (2016). Lessons from domestication: targeting cis-regulatory elements for crop improvement. Trends Plant Sci 21:506-15.

25Nelson DE et al. (2007). Plant nuclear factor Y (NF-Y) B subunits confer drought tolerance and lead to improved corn yields on water-limited acres. Proc Natl Acad Sci 104:16450-5; Qu B et al. (2015). A wheat CCAAT box-binding transcription factor increases the grain yield of wheat with less fertilizer input. Plant Physiol 167:411-23; Yadav D et al. (2015). Constitutive overexpression of the TaNF-YB4 gene in transgenic wheat significantly improves grain yield. J Experiment Bot 66:6635-50.

26Wu J et al. (2019). Overexpression of zmm28 increases maize grain yield in the field. Proc Natl Acad Sci 116:23850-8.

27Chen K et al. (2019). CRISPR/Cas genome editing and precision plant breeding in agriculture. Annu Rev Plant Biol 70:667-97.

28Cavanagh C et al. (2008). From mutations to MAGIC: resources for gene discovery, validation and delivery in crop plants. Curr Opin Plant Biol 11:215-21.

29Huang J et al. (2018). Identifying a large number of high-yield genes in rice by pedigree analysis, whole-genome sequencing, and CRISPR-Cas9 gene knockout. Proc Natl Acad Sci 115:E7559-E67.

30Xu R et al. (2016). Rapid improvement of grain weight via highly efficient CRISPR/Cas9-mediated multiplex genome editing in rice. J Genet Genom 43:529.

31Shen L et al. (2017). Rapid generation of genetic diversity by multiplex CRISPR/Cas9 genome editing in rice. China Sci Life Sci 60:506-15.

32Shen L et al. (2018). QTL editing confers opposing yield performance in different rice varieties. J Integrative Plant Biol 60:89-93; Zhou J et al. (2019). Multiplex QTL editing of grain-related genes improves yield in elite rice varieties. Plant Cell Rep 38:475-85.

33Meyer RS and Purugganan MD (2013). Evolution of crop species: genetics of domestication and diversification. Nature Rev Genet 14:840-52.

34Rodrguez-Leal D et al. (2017). Engineering quantitative trait variation for crop improvement by genome editing. Cell 171:470-80. e8.

35Li T et al. (2018). Domestication of wild tomato is accelerated by genome editing. Nature Biotechnol 36:1160-3; Zsgn A et al. (2018). De novo domestication of wild tomato using genome editing. Nature Biotechnol 36:1211-6.

36Puchta H et al. (1996). Two different but related mechanisms are used in plants for the repair of genomic double-strand breaks by homologous recombination. Proc Natl Acad Sci 93:5055-60; Zhang Y et al. (2016). Efficient and transgene-free genome editing in wheat through transient expression of CRISPR/Cas9 DNA or RNA. Nature Communications 7:1-8.

37Komor AC et al. (2016). Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533:420-4; Hua K et al. (2019). Expanding the base editing scope in rice by using Cas9 variants. Plant Biotechnol J 17:499-504.

38Kang B-C et al. (2018). Precision genome engineering through adenine base editing in plants. Nature Plants 4:427-31.

39Wolter F et al. (2019). Plant breeding at the speed of light: the power of CRISPR/Cas to generate directed genetic diversity at multiple sites. BMC Plant Biol 19:176.

Nina V. Fedoroff is an Emeritus Evan Pugh Professor at Penn State University

Read more:
Next-generation gene-editing technology: Path to a second Green Revolution? - Genetic Literacy Project

BEIJING, April 15, 2020 /PRNewswire/ -- According to the latest news from Science and Technology Daily (April 14th), two COVID-19 inactivated vaccines were just approved for a phase I & II combined clinical trial by the National Medical Products Administration (NMPA) of China, making them the first batch in this category. The two vaccines were developed respectively by Wuhan Institute of Biological Products Co., Ltd of Sinopharm and Sinovac Research & Development Co., Ltd together with research institutes.

This is another piece of good news since the team of Chen Wei, academician at China Academy of Engineering and researcher at Academy of Military Medical Sciences, managed to get clinical trial approval for the recombinant COVID-19 vaccine they developed on March 17th.

"We are taking the lead in developing COVID-19 vaccines in a global perspective," said with pride by Wang Junzhi, academician at China Academy of Engineering. Then he proposed four factors for this achievement: early start, accurate direction, being science-based and collaboration from all parts.

Vaccine is not a distant solution for a current emergency, but rather the most powerful weapon to defeat COVID-19.

China made the decision to accelerate the pace based on rational judgement and organization with the premise of safety assurance. As early on January 21st, the Ministry of Science and Technology (MOST) announced the establishment of an expert group of joint epidemic prevention and control against COVID-19. The expert group was led by Zhong Nanshan, academician at China Academy of Engineering, and consisted of 14 experts. On 22nd, the first eight emergency programs of Scientific Response to COVID-19 were initiated swiftly.

The expert group had decided on five directions for vaccine development: inactivated vaccines, genetic engineering subunit vaccines, adenovirus vector vaccines, nucleic acid vaccines, and vaccines using attenuated influenza virus as vectors. All five directions were to be followed at the same time. Eight teams of advantage in vaccine development were singled out to collaborate on this mission with a detailed plan of work nodes accurate to the day.

Thanks to Chen Wei's accurate judgement and accumulation of knowledge and experience in vaccine development, her team was the first to reach breakthrough achievements. In early February, she suggested that COVID-19 remains a coronavirus despite its possible variation. Therefore, mutual target antigen, pathogenesis and receptor could be identified quickly with the help of bioinfomatics and big data mining once the variation appears. And the vaccine development can be improved swiftly accordingly.

Since the start of the program, Chen Wei's team has conducted research on recombinant COVID-19 vaccine (adenovirus vector vaccine) based on the successful experience in Ebola vaccine development with great speed. On March 17th, the team's recombinant COVID-19 vaccine was approved for clinical trial, which took place one month in advance than expected. By April 2nd, all 108 subjects of phase I clinical trial in Wuhan had been inoculated. On 9th, phase II clinical trial, which has a larger scale and introduces placebo control groups, started recruitment for volunteers.

Meanwhile, all other directions have also made progress.

Lei Chaozi, head of Department of Science and Technology of the Ministry of Education, introduced the current achievements: research on the safety and validity of experimental animal for attenuated influenza vector vaccine is ongoing and pre clinical trial research for vaccine candidates and application for clinical trial are expected by the end of April; animal experiments on mice and rabbits regarding recombinant protein vaccine are being conducted and the technology of large-scale production of vaccine with high quality and purity has been mastered; nucleic acid vaccine development is a new technology being explored by the whole world, but no such vaccine has entered the market yet.

At the same time, Wang Junzhi specifically emphasized the safety issue of the vaccine: "On the one hand, Chinese scientists seek to make full use of time with great effort. On the other hand, they conduct research under scientific laws and ensure the safety and validity of the vaccine. All research and development activities are in accordance with corresponding regulations and technological requirements."

View original content:http://www.prnewswire.com/news-releases/three-chinese-vaccines-against-covid-19-are-on-the-way-301041665.html

SOURCE Science and Technology Daily

Read the original post:
Three Chinese Vaccines against COVID-19 are on the Way - BioSpace

Researchers are interested in genetically modifying trees for a variety of applications, from biofuels to paper production. They also want to steer clear of modifications with unintended consequences. These consequences can arise when intended modifications to one gene results in unexpected changes to other genes. A new model aims to predict these changes, helping to avoid unintended consequences, and hopefully paving the way for more efficient research in the fields of genetic modification and forestry.

The research at issue focuses on lignin, a complex material found in trees that helps to give trees their structure. It is, in effect, what makes wood feel like wood.

Whether you want to use wood as a biofuel source or to create pulp and paper products, there is a desire to modify the chemical structure of lignin by manipulating lignin-specific genes, resulting in lignin that is easier to break down, says Cranos Williams, corresponding author of a paper on the work and an associate professor of electrical and computer engineering at NC State. However, you dont want to make changes to a trees genome that compromise its ability to grow or thrive.

The researchers focused on a tree called Populus trichocarpa, which is a widely used model organism meaning that scientists who study genetics and tree biology spend a lot of time studying P. trichocarpa.

Previous research generated models that predict how independent changes to the expression of lignin genes impacted lignin characteristics, says Megan Matthews, first author of the paper, a former Ph.D. student at NC State and a current postdoc at the University of Illinois. These models, however, do not account for cross-regulatory influences between the genes. So, when we modify a targeted gene, the existing models do not accurately predict the changes we see in how non-targeted genes are being expressed. Not capturing these changes in expression of non-targeted genes hinders our ability to develop accurate gene-modification strategies, increasing the possibility of unintended outcomes in lignin and wood traits.

To address this challenge, we developed a model that was able to predict the direct and indirect changes across all of the lignin genes, capturing the effects of multiple types of regulation. This allows us to predict how the expression of the non-targeted genes is impacted, as well as the expression of the targeted genes, Matthews says.

Another of the key merits of this work, versus other models of gene regulation, is that previous models only looked at how the RNA is impacted when genes are modified, Matthews says. Those models assume the proteins will be impacted in the same way, but thats not always the case. Our model is able to capture some of the changes to proteins that arent seen in the RNA, or vice versa.

This model could be incorporated into larger, multi-scale models, providing a computational tool for exploring new approaches to genetically modifying tree species to improve lignin traits for use in a variety of industry sectors.

In other words, by changing one gene, researchers can accidentally mess things up with other genes, creating trees that arent what they want. The new model can help researchers figure out how to avoid that.

The paper, Modeling cross-regulatory influences on monolignol transcripts and proteins under single and combinatorial gene knockdowns in Populus trichocarpa, is published in the journal PLOS Computational Biology. The paper was co-authored by Ronald Sederoff, a professor emeritus of forestry and environmental resources at NC State; Jack Wang, an assistant professor of forestry and environmental resources at NC State; and Vincent Chiang, a Jordan Family Distinguished Professor Emeritus and Alumni Outstanding Research Professor with the Forest Biotechnology Group at NC State.

This work was supported by the National Science Foundation Grant DBI-0922391 to Chiang and by a National Physical Science Consortium Graduate Fellowship to Matthews.

Link:
Study: Better Predicting the Unpredictable Byproducts of Genetic Modification - Tdnews

Documentary "Human Nature" examines how gene editing can help - and hurt - humanity.

If youre familiar with the Replicates from Blade Runner, the velociraptors from Jurassic Park or the genetic engineering so chillingly laid out in Aldous Huxleys novel Brave New World, youll be fascinated by how much science fiction has become science fact in Adam Bolts Human Nature. And its all due to CRISPR (pronounced crisper), a gene-altering technology that not only could facilitate designer babies, but possibly play a central role in putting the clamps on another acronym, COVID-19.

That timeliness is obviously on the side of Human Nature, a snazzy-looking documentary using sparkling graphics and top geneticists, journalists and one very adorable sickle-cell anemic to spell out a complicated subject in compelling, easy-to-grasp terms. But that same timeliness also works against it, given how now is not an advantageous moment for the films commercial aspects amid a landscape of shuttered theaters and a frightened populace whod like to avoid anything to do with medicine and science as sources of entertainment.

Yet, that double-edged sword fits snuggly in the wheelhouse of CRISPR (short for clustered regularly interspaced short palindromic repeats), a microorganism able to locate and repair defective DNA, as well as fend off invading viruses like COVID-19 by acting as a defense shield mimicking the offenders own DNA. But like the Internet, a revolutionary breakthrough for which CRISPR is often compared, theres a serious downside involving the morality of whether humans should have the right to, as the film calls it, play God. Namely, should parents be allowed to treat an embryo the same way theyd approach ordering a pizza? Well have the regular with blue eyes, blonde hair and an IQ of Einstein. Oh, and could you throw in some immense athletic ability, too?

Clearly, CRISPR has the potential to put us at the mercy of the type of mad scientists weve become accustomed to in just about every Bond film ever made. One geneticist, whose very name, Jennifer Doudna, includes DNA, admits having had a nightmare in which she comes face-to-face with Adolf Hitler! Are we willing to toy with the very real prospect of creating a master race?

Thats just one of the troubling questions Bolt confronts you with while weighing the pros and cons of a new frontier brimming in possibilities and danger. Personally, I come down on the side of CRISPRs benefits, particularly after meeting David Sanchez, a teen with sickle cell thats spent about half of his young life in hospitals receiving precious blood transfusions. Hes smart, personable and amazingly brave, so much so, you cant help but be all in when CRISPR offers him a chance at a more normal life. Yet, hes just as quick to recall to how hes learned to embrace -- even appreciate -- his illness because its made him a better, more resourceful kid, insights he would not have acquired had CRISPR been available when he was in utero. See? Hes torn, too.

Do we embrace a discovery wielding the promise of curing and preventing cancers and birth defects, or shun it for its ability to rob us of our unique individuality? Its a compelling argument I frankly wish Bolt had expanded more upon in his movies all-too-brief 90 minutes. But whats here is more than enough to spark a multitude of kitchen-table conversations about where we should set the limits on science, and more importantly, who should be making those decisions.

Given the disarray COVID-19 has put the world in, now probably isnt the time for us to evaluate, especially when CRISPR could well determine our fate by ridding our planet of a crippling plague. But what about after? Will, as Trump is fond to say, the cure be worse than the disease? Its a question for which Human Nature holds no answers, only utopian and despotic possibilities well be forced to uneasily choose between when and if the time comes.

See the original post here:
Movie review: Doc Human Nature strikes a nerve in the age of coronavirus - The Patriot Ledger

Alain Mrieux, founder of BioMrieux.

Latest update: April 1, 2020, at 4:47 pm ET.

Businesses around the world are shifting into overdrive to help battle the coronavirus, providing everything from rubber gloves and ventilators to diagnostic tools and, hopefully soon, vaccines. While the pandemic continues to wreak havoc, large corporations and small businesses are developing creative solutions to halt the spread of the virus.

Just as automakers famously shifted to make tanks and planes during World War II, todays global giants LVMH, Ford and GE to name a few are retooling their production lines to help make everything from hand sanitizers to respirators. On the medical front, there are more than three dozen COVID-19 vaccines under development, a smart move considering that two out of every three vaccines for infectious diseases fail, according to a study by the Massachusetts Institute of Technology.

Forbes will continue to update this list of private companies and how they are stepping up to fight the COVID-19 pandemic:

Testing:

Abbott Laboratories: Abbott Park, Illinois healthcare firm obtained emergency FDA authorization for its 5-minute coronavirus testing kit on March 27, with plans to start manufacturing 50,000 kits a day.

Alphabet: Through its healthcare arm Verily, Googles parent company launched a website where users can find nearby testing sites in four California counties.

Jeff Bezos.

Amazon: Jeff Bezos retail behemoth invested $20 million in the Amazon Web Services Diagnostic Initiative, which aims to speed up delivery of COVID-19 tests to the market.

BioMrieux: French biotech company, founded by billionaire Alain Mrieux,received emergency FDA approval for its subsidiarys new testing kit, which cuts testing times for the virus down to 45 minutes.

Carbon: California-based 3D printing unicorn backed by Russian tech investor Yuri Milner will soon be distributing testing swabs and face shields to hospitals in the Bay Area.

Cepheid: Sunnyvale, California molecular diagnostics company gained emergency FDA authorization for its new 45-minute COVID-19 testing kit.

Copan Diagnostics: Family-owned company located at the heart of Italys hard-hit Lombardy region makes diagnostic swabs for testing, airlifting 500,000 swabs to the U.S.

DiaSorin: Italian biotech company owned by billionaire Gustavo Denegri obtained emergency authorization from the FDA for its new 60-minute testing kit for COVID-19.

Mammoth Biosciences: South San Francisco-based biotech startup, founded by three 30 Under 30 alums, prototyped a rapid test by using the gene-editing tool Crispr to detect the disease.

Mesa Biotech: San Diego biotech business obtained FDA approval for its new 30-minute testing kit for COVID-19.

Puritan Medical Products: Maine-based diagnostic maker, one of the worlds largest makers of diagnostic swabs along with Italys Copan Diagnostics, is reportedly increasing production to make one million COVID-19 testing swabs a week.

Treatments:

AbbVie: North Chicago-based, publicly traded pharma firm is collaborating with authorities in the EU, the U.S. and China on experimental use of its HIV drug lopinavir/ritonavir to treat COVID-19.

AIM Immunotech: Florida-based pharmaceutical company announced on March 9 it would begin experimental testing of its chronic fatigue syndrome drug rintatolimod as a treatment for COVID-19 in Japan, at the National Institute of Infectious Diseases and the University of Tokyo.

Algernon Pharmaceuticals: Vancouver-based pharmaceutical firm is requesting FDA approval to begin trials of its chronic cough medication ifenprodil as a treatment for COVID-19.

AlloVir: Houston-based cell and gene therapy company is collaborating with Baylor College of Medicine to discover and develop T-cell therapies to fight COVID-19.

Apeiron Biologics: Vienna-based biotech firm started small-scale trials of its immunotherapy treatment on COVID-19 in China in February.

Ascletis: Hangzhou, China pharmaceutical company announced results of clinical trials of its antiviral drug danoprevir on COVID-19 patients in China; the small-scale study found that danoprevir combined with ritonavir is safe and well tolerated in all patients.

Bioxytran: Boston-based biotech outfit is developing a viral inhibitor to treat COVID-19.

Celltrion: South Korean healthcare firm is developing an antiviral treatment for COVID-19 as well as rapid self-testing kits that would provide results within fifteen to twenty minutes.

Cocrystal Pharma: Bothell, Washington pharma outfit is developing antivirals to treat COVID-19 using patents it recently acquired from the Kansas State University Research Foundation.

CytoDyn: Vancouver, Washington biotech firm announced preliminary results from three days of testing its antiviral drug leronlimab on COVID-19 patients in New York; the company stated in a press release that test results from the first four patients suggests immunological benefit within three days following treatment with leronlimab.

Eli Lilly: Indianapolis pharma company is partnering with Vancouver-based biotech outfit AbCellera to develop antibody-based treatments for COVID-19.

Emergent BioSolutions: Maryland drugmaker is developing treatments derived from the antibodies found in the blood of people who tested positive for the disease.

EUSA Pharma: British pharmaceutical firm initiated trials of its siltuximab antibody treatment on COVID-19 patients at the Papa Giovanni XXIII hospital in Bergamo, Italy; the company released initial data on April 1 showing that one third of patients experienced clinical improvement with reduced need for oxygen support and a further 43% saw their disease stabilise.

Fujifilm Toyama Chemical: Tokyo-based conglomerates flu drug favipiravir has shown promising results in early clinical trials on COVID-19 patients in China, and the company is investing $83 million in its biological manufacturing capabilities.

Gilead: The Californian biotech giant initiated clinical trials in March for its antiviral drug remdesivir on patients in the U.S.

Harbour BioMed: Cambridge, Massachusetts biomedical firm announced a collaboration with New Yorks Mount Sinai Health System to develop new human antibodies to treat COVID-19.

I-Mab Biopharma: Shanghai-based biopharma outfit announced it would begin clinical trials of its TJM2 antibody treatment on COVID-19 patients in the United States, with plans to expand to other countries affected by the pandemic.

ImmunoPrecise: Canadian life sciences company is teaming up with New York-based AI startup EVQLV Inc on researching antibody-based therapies and a vaccine for COVID-19.

Innovation Pharmaceuticals: Wakefield, Massachusetts biopharma firm is researching the use of its drug brilacidin part of a category of investigational new drugs called defensin mimetics, which could have antimicrobial effects as both a treatment and a vaccine for COVID-19, in separate efforts with a major U.S. university and with the Department of Health and Human Services.

ISR Immune System Regulation: Swedish immunotherapy firms subsidiary, ISR HBV, is conducting toxicological studies to determine whether its Immunolid ISR50 treatment could be used against COVID-19.

Kamada: Israeli pharmaceutical company is working on an antibody-based treatment for COVID-19 using the blood plasma of patients who recovered from the disease.

Mateon Therapeutics: Californian biopharma firm is testing a number of antiviral drugs as potential treatments for COVID-19 and is preparing to submit an application to the FDA in order to begin clinical trials on patients.

Merck KGaA: Darmstadt, Germany-based pharma multinational donated a supply of its multiple sclerosis drug interferon beta-1a to the French National Institute of Health and Medical Research in Paris for clinical trials on COVID-19 patients. The companys North American life sciences arm, MilliporeSigma, is supplying several vaccine efforts with reagents and other essential raw products for vaccine development.

Mesoblast: Australian medical firm is working with authorities in the U.S., Australia, China and Europe to evaluate the use of its remestemcel-L drug to treat COVID-19.

Mylan: Pennsylvania-based pharmaceutical firm restarted production of hydroxychloroquine, a drug used to fight lupus, malaria and arthritis, at its West Virginia factory; the drug is being tested as a treatment for COVID-19 in human trials in New York.

Pluristem Therapeutics: Haifa, Israel-based medical company is developing a cell-based therapy to treat COVID-19, announcing on March 30 it had dosed three Israeli patients under a compassionate use program, with plans to enroll more.

Leonard Schleifer.

Regeneron Pharmaceuticals: Westchester, New York biotech outfit, run by billionaires Leonard Schleifer and George Yancopoulos, is conducting clinical trials of its rheumatoid arthritis drug sarilumab, developed with French firm Sanofi, on patients in New York.

Roche: Swiss pharma titan, part-owned by billionaire Maja Oeri, is testing its arthritis drug tocilizumab to treat patients in China and received FDA approval to begin U.S. trials.

Roivant Sciences: Swiss pharma company is working with U.S. authorities to begin trials of its antibody treatment, gimsilumab, on COVID-19 patients.

Takeda: Japanese medical firm is working on hyperimmune therapy using blood plasma from previously infected patients.

Vir Biotechnology: The San Francisco-based firm is collaborating with Biogen and Chinese medical firm WuXi Biologics to manufacture antibodies that could treat the virus.

Vaccines:

AJ Vaccines: Danish vaccine developer is working on a COVID-19 vaccine that could hit the market in 2021.

Altimmune: The company is developing a novel intranasal vaccine for the coronavirus, making it one of three firms based in Gaithersburg, Maryland along with Emergent Biosolutions and Novavax thats working on treatments and vaccines for COVID-19.

Arcturus Therapeutics: San Diego-based vaccine maker is developing a COVID-19 vaccine with researchers at the Duke-National University of Singapore medical school in Singapore.

Biocad: Russian drug developer is researching a COVID-19 vaccine, with animal trials scheduled for late April.

Thomas and Andreas Struengmann.

BioNTech: German biotech firm backed by billionaire twins Thomas and Andreas Struengmann is working to develop a coronavirus vaccine in partnership with Pfizer and Fosun Pharma, chaired by billionaire Guo Guangchang.

CanSino Biologics: Tianjin, China-based pharma company isstarting clinical trials for its COVID-19 vaccine, using the vaccine technology deployed to develop the Ebola vaccine.

Codagenix: Melville, New York biotech firm is teaming up with the Serum Institute of India to develop a live-attenuated COVID-19 vaccine, which uses a live but weakened form of the virus.

Dietmar Hopp.

CureVac: German firm, funded by billionaire Dietmar Hopp and the Bill and Melinda Gates Foundation, received $87 million from the European Commission to scale up development of its coronavirus vaccine.

Dyadic: Jupiter, Florida company is collaborating with the Israel Institute for Biological Research on both treatment and a vaccine against COVID-19, using the firms gene expression platform.

Dynavax: Emeryville, California vaccine maker is working with the Coalition for Epidemic Preparedness Innovations (CEPI) and the University of Queensland to develop a COVID-19 vaccine.

EpiVax: Providence-based immunology firm is working with the University of Georgia and Miramar, Florida biotech outfit Generex on separate COVID-19 vaccine efforts.

ExpreS2ion: Danish biotech company received a grant of nearly $1 million from the European Union to develop a vaccine for COVID-19.

GeoVax: Atlanta-based medical company is collaborating with Wuhan-based BioVax to jointly produce a COVID-19 vaccine.

GlaxoSmithKline: British pharma titan is partnering with CEPI and Chengdu, China-based Clover Pharmaceuticals to use its pandemic vaccine adjuvant platform which boosts the immune response in patients receiving a shot to speed up development of COVID-19 vaccines.

Greffex: Houston-based genetic engineering firm is preparing to begin animal trials for its COVID-19 vaccine.

Heat Biologics: North Carolina biopharma company is developing a COVID-19 vaccine with the University of Miami.

iBio: Newark, Delaware biotech upstart is collaborating with Beijing-based CC-Pharming on the rapid development of a COVID-19 vaccine.

Inovio: Plymouth Meeting, Pennsylvania biotech business received $11.9 million in funding from the Department of Defense to rapidly produce a DNA vaccine for COVID-19 with drugmaker Ology Bioservices.

Johnson & Johnson: The companys pharma unit, Janssen, will start manufacturing its vaccine developed with the Department of Health and Human Services this month, with human trials set to begin by September and a public rollout hoped for early 2021. The company and the federal government are investing more than $1 billion in the vaccine effort.

Medicago: Quebec City-based biotech company received more than $7 million from the Canadian and Quebec governments to fund development of its COVID-19 vaccine.

Moderna: Massachusetts biotech company was the first tobegin human trials of its vaccine on March 16 in Seattle and could deploy it to health workers for emergency use by the fall.

Novavax: Maryland-based vaccine maker received $4 million in funding from CEPI to accelerate development of its vaccine candidates, with clinical trials expected in the late spring.

Sanofi: French medical firm is working with the federal government and Massachusetts-based Translate Bio to expedite its coronavirus vaccine, using technology previously used to develop one for SARS.

Sorrento Therapeutics: San Diego-based biotech firm is teaming up with Cambridge, MA gene therapy company SmartPharm Therapeutics to develop a gene-encoded COVID-19 vaccine; its also working with Chinese drugmaker Mabpharm on a fusion protein treatment for the disease.

Takis Biotech: Italian startup with just 25 employees is developing a vaccine with Stony Brook-based Applied DNA Sciences, with plans to begin human trials before the end of the year.

Themis Bioscience: Austrian biotech firm is part of a group, with the Institut Pasteur and the University of Pittsburgh, which received $4.9 million in initial funding from CEPI to build a COVID-19 vaccine modeled on the vaccine for measles.

Tonix Pharmaceuticals: New York-based pharma outfit is researching a potential COVID-19 vaccine based on the virus that causes horsepox.

Vaxart: San Francisco vaccine manufacturer Vaxart is working with Emergent Biosolutions to develop and manufacture an oral vaccine that can be taken as a tablet.

Vaxil: Israeli biotech startup began preclinical trials for its COVID-19 vaccine candidate.

Zydus Cadila: Indian pharma company announced it would fast-track development of a COVID-19 vaccine in February.

Protective Equipment And Sanitizer:

Anheuser-Busch InBev: The worlds largest beer company is making more than one million bottles of hand sanitizer from surplus alcohol at its breweries around the world.

Giorgio Armani.

Armani: Billionaire Giorgio Armanis luxury fashion brand converted all production at its Italian factories to manufacture single-use medical overalls on March 26.

Bacardi: The Bermuda-based spirits giant converted production at nine production facilities in Mexico, France, England, Italy, Scotland, Puerto Rico and the continental U.S. to make hand sanitizer.

BrewDog: Independent beermaker is making hand sanitizer at its distillery in Scotland.

Bulgari: The Italian luxury jeweler is manufacturing hand sanitizer with its fragrances partner, ICR, with plans to make hundreds of thousands of bottles by May.

Sandro Veronesi.

Calzedonia Group: Italian retail clothing group, owned by billionaire Sandro Veronesi, converted production at several plants in Italy and Croatia to manufacture masks and medical gowns, with initial production of 10,000 masks a day.

Cantabria Labs: Spanish health products and cosmetics firm converted production at one of its factories to make hand sanitizer.

Consomed: Tunisian mask and medical equipment maker put all of its workers, more than 70% of which are reportedly women, on quarantine inside the companys Kairouan factory to maximize production of protective gear.

Decathlon: Sporting goods empire founded by French billionaire Michel Leclercq partnered with Isinnova, a small engineering and design firm based in Italy, to convert snorkeling masks into respirators.

Diageo: The maker of Johnnie Walker whisky and Smirnoff vodka donated two million liters of ethyl alcohol, a byproduct of the distillation process, to hand sanitizer manufacturers.

Fanatics: Billionaire Michael Rubins online sportswear retailer converted its baseball jersey factory in Pennsylvania to make masks and gowns for medical workers.

Fiat Chrysler Automobiles: The multinational automaker announced on March 23 it would begin installing capacity to produce masks, which will be initially distributed in the U.S., Canada and Mexico.

Fippi: Italian diapers producer worked with the Lombardy region and the Polytechnic University of Milan to convert its factory to make up to 900,000 masks a day, which will go to frontline health workers facing a devastating outbreak in the region.

Go here to read the rest:
Coronavirus Business Tracker: How The Private Sector Is Fighting The COVID-19 Pandemic - Forbes

How prepared do you think we were for this moment of social distancing and for this global moment of hunkering down amidst uncertainty?In terms of social distancing, weve been social distancing; weve been virtualizing our lives since at least the advent of the telegraph in the 19th century. We have this idea of distance even now, where were communicating from away and communicating to others. But we also, as humans, have this deep need for physical connectivity. We are not virtual beings. And so, emotionally, were not ready for it. All of these structures for physical connectivity are gone, at least temporarily. Were almost in this Battlestar Galactica remake moment where were having to reconceptualize space and community. Its not that we will become un-physical beings, but were gonna have to figure out different ways of virtually sharing emotion and connectivity, at least until this danger passes.

Thats why organizations like PEN that are so focused on values are so critical, because these are the conversations that we have to have. Were going to have this incredible technology, but its up for grabs whether these technologies will be used to help or harm us.

You wrote at CNN.com about the human need for intimate physical connectivity. Can technology be a substitute for that? It seems like probably not.It cant be a substitute, but it can be a complement. And again, in our best possible world, I, for one, would love to live in some kind of hippie commune with real people there, and I also live, like many people, this global life where my friends and contacts are distributed around the world. I think we need to find that balance. But at times like this, our lives are becoming and feeling more virtual. And yes, theres a loss, and I think many of us are mourning that loss. But this is the world that we have now, and we have to make the most of it. Theres a lot of simple things that people can do. Make a list of all the people who you love and care about in your life, all the people who you think may be feeling isolated or alone, and just create a schedule of reaching out to them. My girlfriend and I are doing a virtual tea party with friends on Sunday where were gonna make tea, theyre gonna make tea, were gonna connect on FaceTime. We have to think of how we might do things differently. But its also not the case that when this crisis ends, society is just going to snap back to where it was, and were going to say, Wow, that was a crazy experience. Theres something happening now that is going to last beyond this.

What are some things that could be irrevocably different about our culture and the way we work and live, as a result of this moment?Were for sure not going fully back on virtualization. Were going to do things differently. Our sense of space is going to be different. A lot of people who are now working from home arent going to go back to physical offices because once companies figure out how they can work in this way, itll just be cheaper to have people stay at home. Were certainly going to change the way we think about global public health. If you asked a regular person, Wouldnt it make sense to have a super empowered World Health Organization with a global surveillance system that whenever any trip wire was hit, youd have an emergency response team that would fly to wherever that was and they would set up a command center and do what needed to be done? They would say, Yeah, dont we have that? And the answer is we dont. Because we have starved organizations like the WHO, because we have states that are demanding a level of control that doesnt make sense in our world of global challenges. One of the things that Im working on very, very actively now is imagining a third leg of the global political stool in addition to states and international institutions, and that is the democratic expression of the needs of our common humanity. It seems like its this big, crazy idea. But in these negotiations, no one is saying, Hey, climate change affects all of us; destroying our oceans affects all of us; global pandemics affect all of us. Who is standing up to help humanity? And thats what I think we need now.

I feel like Im at war from the battlestation of my office here on 81st Street in New York, so Im pretty focused on reading what I need to read now.

In Hacking Darwin, you wrote about genetics, you wrote about changing our genetic identity, perhaps to yield cures for diseases. Are you more or less optimistic about the potential for genetic science and cures than you were before?Im extremely optimistic. We are facing an enormous challenge today, but we now have almost godlike capacities to read, write, and hack the code of life. And those tools, Im firmly convinced, are going to save us, and were going to figure out treatments and were gonna have a vaccine not just for this, but for all kinds of challenges in the future. But these technologies dont come with a built-in value system. All technologies are value-neutral. Its up to us to determine what are the values that will guide the application of our most powerful technologies, and thats the issue. Thats why organizations like PEN that are so focused on values are so critical, because these are the conversations that we have to have. Were going to have this incredible technology, but its up for grabs whether these technologies will be used to help or harm us.

Finally, what are you reading, watching, or listening to right now?I would advise people at times of crisis like this to read poetry and literature. Im trying to do a little bit of that, but Im just all in and obsessed. Just last night I finished this incredible book, Spillover, by the amazing journalist David Quammen. And thats about zoonotic viruses like this, and our experiences in the past. Im now reading Betrayal of Trust by Laurie Garrett, which is about the destruction of our public health infrastructure. So when this is done, Im just going to beand I myself am a novelistback to reading the novels that I love so much. Maybe Ill read Proust and start thinking about Maman and her madeleine. But for now, I feel like Im at war from the battlestation of my office here on 81st Street in New York, so Im pretty focused on reading what I need to read now.

Wed like to know what books youre reading and how youre staying connected in the literary community. Click here to leave a voicemail for us. Your message could end up on a future episode of this podcast!

LEAVE A MESSAGE

Read the original here:
The PEN Pod: Reimagining the Future with Jamie Metzl - PEN America

The quarter was brutal to say the least for most asset classes amid the coronavirus (COVID-19) pandemic. The S&P 500 Index was down about 20% for the quarter.

Amid the market mayhem, some health care stocks defied the downturn, thanks to announcements concerning development of drug/vaccine/diagnostic tests for new coronavirus.

Focusing on biotechs (leaving out diagnostics stocks), here the top five winners and losers for the quarter.

Benzinga is covering every angle of how the coronavirus affects the financial world.For daily updates,sign up for our coronavirus newsletter.

Genprex Inc (NASDAQ: GNPX): (+656.25%)

After ending 2019 in penny stock territory, shares of this gene therapy company began to gain ground after the company announced Fast Track Designation for its immunogene therapy in combination with AstraZeneca's(NYSE: AZN) Tagrisso for treating lung cancer. The momentum accelerated after it signed an exclusive agreement to license a diabetes gene therapy from the University of Pittsburgh.

After topping $7 in late February, the stock came off the highs amid the COVID-19 sell-off and managed to end the quarter with huge gains.

Vaxart Inc (NASDAQ: VXRT): (+405.71%)

Vaxart is a COVID-19 play and much of the quarter's gains were achieved on the back of the experimental oral vaccine candidate it's developing in partnership with Emergent Biosolutions Inc (NYSE: EBS).

Ibio Inc (NYSE: IBIO): (+324%)

Ibio, which develops human therapeutic proteins using advanced genetic engineering, joined the fray for a COVID-19 vaccine, which explains the surge in the stock.

Novavax, Inc. (NASDAQ: NVAX) (+241.2%)

Novavax was the beneficiary of dual catalysts: a COVID-19 vaccine in development and positive late-stage readout for its flu vaccine.

Trillium Therapeutics Inc (NASDAQ: TRIL): (+192.23%)

Thisimmuno-oncology company did not have much developments to justify its gain for the quarter.

Following a jump of about 63% in a single session in late February, the company issued a statement thatsaid "it is not aware of any material, undisclosed information related to the company that would account for the recent increase in the market price and level of trading volume of its common shares."

Related Link: Attention Biotech Investors: Mark Your Calendar For These April PDUFA Dates

Milestone Pharmaceuticals Inc (NASDAQ: MIST): (-88.51%)

This cardiovascular-diseases-focused biopharma was cruising along fine until COVID-19 sell-off started in March. The real punch came from an adverse clinical readout.

Novan Inc (NASDAQ: NOVN): (-84.97%)

Novan, which leverages on nitric oxide's naturally occurring anti-microbial and immunomodulatory mechanisms of action to treat various diseases, fell steeply at the start of the year. The trigger was a late-stage readout of its SB206 in molluscum contagiosum, which showed that the pipeline asset did not achieve statistically significant results for the primary endpoint.

The stock did not recover from this onslaught.

Acasti Pharma Inc (NASDAQ: ACST): (-84.49%)

Acasti also succumbed to a negative clinical readout for its lead prescription drug candidate CaPre, which did not achieve statistical significance for the primary endpoint of a late-stage study that evaluated it for treating elevated levels of triglycerides.

The company is now seeking FDA guidance for unblinding data from another Phase 3 study, and therefore expects a delay in reporting of topline results until the third quarter.

Salarius Pharmaceuticals Inc (NASDAQ: SLRX): (-81.98%)

This oncology-focused biotech gradually declined through the quarter, with some steep sell-off materializing amid its presentation at the BIO CEO & Investor conference in mid-February.

Amarin Corporation plc (NASDAQ: AMRN): (-81.34%)

Amarin shares, which ran up ahead and after the late-December FDA verdict on its application seeking label expansion for its fish oil pill, pulled back in January. The weakness intensified through the market meltdown. A negative court ruling sent the stock reeling this week.

2020 Benzinga.com. Benzinga does not provide investment advice. All rights reserved.

See the original post here:
10 Biotech Winners And Losers In Q1 - Benzinga

In the field of prevention, the work of Mexican molecular medicine researcher Laura Palomares stands out. And today, her team is developing a vaccine against SARS-CoV-2, based on the work they have been doing in recent years against dengue and zika.

I am convinced that the only way that we are going to be able to respond to this type of pandemic in a timely manner is going to be using platforms. I am referring to a vaccine, for which we already have the entire production, development, stability train, etc. , said the chemical engineer from the Instituto Tecnolgico y de Estudios Superiores de Monterrey (ITESM), that holds a masters in Biotechnology, and a doctorate in science from UNAM.

Many times we think that the laboratory is going to discover a vaccine to cure the patient, and it is not like that. This type of vaccine requires a lot of time and a lot of effort in developing the processes for production and characterization, before reaching the final patient, Laura Palomares added.

With this idea in mind, the also researcher at the Institute of Biotechnology (IBt) of UNAM has promoted the development of one of these technological and methodological platforms focused on the aforementioned Zika and Dengue viruses, conditions particularly significant for Mexico due to their high numbers of contagion, every year in different parts of the country.

The result has been a vaccine created with recombinant DNA technology, which Palomares calls a chimera.

Lets put it in simple words, for people to understand: If we take away from the platform the zika and dengue viruses, and we put the coronavirus there, that way we can get a vaccine against SARS-Cov-2, says the member of the University Commission for Attention of the Coronavirus Emergency.

What took us two years in genetic engineering, adding on and taking off proteins, understanding how these capsids were going to be assembled, characterizing them, etc., all that we had already done. So now, we are replacing that with SARS-CoV-2, and that is precisely why we have advanced so much right now , Palomares continued.

The approach to the development of vaccines through platforms has also been the route taken by two vaccines against Covid-19 in the world that are currently under clinical evaluation: that of the North American company Moderna and that of the Chinese company CanSino Biologics, stated the expert.

The coronavirus vaccine is in the testing phase in animal models, a process in which the Zika and dengue vaccine has already been evaluated. If everything progresses positively, Palomares estimates that the first human tests could be carried out in three years.

In the case of the SARS-CoV-2 vaccine that she and her team are currently developing, they plan to collaborate wth the Mexican company Liomont, which has a manufacturing plant that would allow the production of this vaccine, this way Mexico does not have to depend on transnational companies.

So this pandemic is obviously terrible for us, because it is affecting the health of a large part of the population, but also a great opportunity to raise awareness, the researcher concluded.

comments

Continued here:
Mexico is already testing its own Covid-19 vaccine - The Yucatan Times

Pharma and biopharma companies dont want to work on their relationships. These companies want their relationships to work for them. Fair enough. Still, when it comes to relationships with contract manufacturing and drug development organizations (CDMOs), pharma and biopharma companies cant avoid intimacy. These relationships are rewarding to the extent pharma and biopharma companies are clear about their needs and the kinds of associations consistent with those needs.

Typically, the most pressing need is keeping costs down. But other needs are important, too. These include expertise with specialized technologies, challenging drugs, and complex formulations. Identifying needs will help pharma and biopharma companies decide whether their CDMOs should help with discrete activities or provide complete, end-to-end services. Pharma and biopharma companies may also want their CDMOs to help with business strategy and regulatory compliance.

Besides identifying potentially compatible CDMO partners, pharma and biopharma companies need to build CDMO relationships characterized by mutual trust. Here again, clear communication is essential. It can help both parties in a CDMO relationship resolve misunderstandings and overcome unanticipated challenges together. For a fuller discussion of the ways CDMO relationships can benefit from clear communication, see the rest of this article, which presents various pointers and perspectives from CDMO experts.

Thierry Cournez is head of end-to-end solutions at MilliporeSigma, which offers a comprehensive portfolio of high-quality products and services, including testing services, for biopharmaceutical development. According to Cournez, most emerging biotech companies that have very early data and need to take their molecule to commercialization dont have all the expertise in-house that they need to navigate the entire process. One major trend is complete services, as opposed to la carte offerings.

MilliporeSigmas Plug & Play Upstream Development Service eliminates the need to work with multiple vendors for upstream development, relieving bottlenecks and reducing time to clinic. The service covers cell line development from DNA transfection to cell banking. Process development activities, which run in parallel, start when the company receives material from the first clones.

Cournez says that two services that will continue to be important in pharmaceutical development are process development and analytical services. A robust process is critical for manufacturing success, he explains, and analytical services are the foundation that supports the entire life cycle of biologics.

A trend toward all-in-one CDMO services has also been observed by Richard Shook, director of drug product technical services and business integration at Cambrex. Any time a client has to go to multiple vendors, it creates a lot of seams and communication problems, he points out. A lot of dots are not connected. Critical items can be lost, especially internal knowledge. When a client works with a single vendor, he stresses, the partners create a knowledge base that can be carried forward with the project. Cambrex provides drug substance, drug product, and analytical services across the entire drug lifecycle.

Fujifilm Diosynth Biotechnologies (FDB) is a division of Fujifilm that focuses on biopharmaceutical contract manufacturing, especially drug substances for biologics. That includes cell culture and fermentation, development and manufacturing, and advanced therapies like gene therapy. Fujifilms director of strategic business development, Daniel DeVido, PhD, says there is growing interest in gene therapy products and gene modified cell therapies.

In the area of viral vectors, new products on the market such as Luxturna (from Spark Therapeutics) and Zolgensma (from Novartis) have moved that sector of the industry forward. Newly approved chimeric antigen receptor (CAR) T-cell therapies, such as Kymriah (from Novartis) and Yescarta (from Kite Pharma) are also injecting energy into the field. And monoclonal antibodies have been going strong for the last 10 to 15 years, with approximately 80 therapies approved and on the market.

The industry is well funded right now, DeVido points out. A lot of companies are pushing candidates forward.

That increased demand for cell culture services brings new technical challenges. Everybodys looking for increased titers, DeVido emphasizes. For gene therapy, yields and titers are much less than they are for cell culture, so everybodys looking for the next thing that will get gene therapy to produce on the scale that monoclonal antibodies are on now.

Lonza offers a range of CDMO services. Karen Fallen, the companys head of mammalian and microbial development and manufacturing, says that Lonza works with companies from several different segments, including small and virtual companies that have limited in-house resources and capabilities. A lot of them are really focusing on the science, she notes. Theyre looking for preclinical and clinical services.

In Lonzas view, some of the trends among the smaller companies are due to larger Series A financings. In past years, Series A deals would have been $10 or $15 million, but now they are running higher, up to $70 or $80 million. They have different ambitions now, Fallen points out. They want and are able to take the molecule further along the supply chain, even to launch. They want to stay with Lonza longer before they partner up with large pharma and/or out-license these molecules. She adds that Lonzas customers also have more complex molecules in their pipelines.

Lonzas other big segment consists of large pharma companies. They have assets, and they have experience, she says. What theyre looking for now is newer technologies, with newer modalitiesbioconjugation, highly potent small molecules, or cell and gene therapies, for example.

Almac Group provides an extensive range of contract development and manufacturing services across the drug development life cycle. The increased interest in pediatric formulations is driving a demand for mini-tablets, especially those in stick-pack dosage form. The rapidly expanding oncology space, by its nature, creates a need for CDMOs that have extensive capabilities in processing highly potent active pharmaceutical ingredients at the small-to-medium scale.

Were seeing an industry trend toward higher value, lower volume products, says Jonas Mortensen, vice president of business development at Almac. Our clients are asking us to take on commercial supply of their product, often at, or close to, the same scale we had previously provided for their clinical studies.

To meet these new needs, Almac has installed multiple stick-pack machines across its sites in the United Kingdom and the United States. Almac is also finalizing the qualification of a dedicated suite of eight processing rooms and equipment solely designed for, and dedicated to, processing of highly potent active pharmaceutical ingredients.

Mortensen anticipates that some near-term trends in CDMO services will include supply chain risk mitigation, end-to-end services, and GMP floor space. CDMOs, he points out, are increasingly being asked to demonstrate their ability to support multisite supply strategies through global facilities or act as a secondary site of manufacture.

Communication is a common theme when it comes to recommendations for working with a CDMO. MilliporeSigmas Cournez says that biotech companies should choose a CDMO that has the most experienced people in-house. Doing so can help biotech companies avoid having to deal with multiple vendors. He also recommends having a dedicated project manager who can provide transparent communication with the vendor and connect with subject matter experts in case of unexpected changes.

Good communication also contributes to transparency in a project. Project transparency is really important, insists Cambrex Shook. That can be limited due to the competitive landscape of the project.

If problems arise during project execution, ownership and communication is really important. If its not there, losses occur and there are timeline setbacks. This could impact the scope, and once you get off scope, [it takes] money and resources to get back on track.

An illustration of the importance of communication comes from Catalent, a company that offers a range of CDMO services, including its recently introduced GPEx Boost technology for cell line development. Michael Riley, vice president and general manager of biologics at Catalent, says that in a program the company is currently working on, a customer was on a highly accelerated path to a product filing for a fast-track product. Catalent was working with regulatory authorities to characterize the companys manufacturing process and move toward validation of that process. To do that, Riley explains, we had to have very robust conversations between multiple functions within our organization and their organization from a quality and development standpoint.

Trust can be a delicate issue in relations between a CDMO and a customer. To illustrate this point FDBs DeVido describes a face-to-face discussion that the company had with one of its customers. This discussion, which took place in FDBs office in Cambridge, MA, resolved some contractual disagreements. We were able to sit around the table and go through the legal issues, DeVido recalls. We cleared up a lot very quickly.

When you sit down face to face and have good discussions, he says, everyones a little more comfortable. Even though people may feel theyre not completely safeguarded from a one-in-a-million occurrence, they may feel comfortable the two parties are going to work together through whatever the issue is.

DeVido said that once youve selected a CDMO, its important to be transparent and trust the company. Youve done your due diligence, he proposes. Now trust your selection and the system theyre operating in.

Benefits of working with an experienced vendor can go beyond development and manufacturing. Cournez says that in one instance, an emerging biotech customer had the opportunity to engage in licensing discussions with a large pharmaceutical company. Because the emerging biotech was small, we hosted the large pharma company at one of our sites and ran the due diligence, which was a great success, he relates. This former emerging biotech now funds many different programs because of the success of their first molecule.

Some vendors warn that business strategies can backfire. Focusing too much on price and speed to market can be risky when researching or working with CDMO/CMO partners, according to Cournez. The service provider must simplify the process and reduce touchpoints throughout the process.

Mortensen says that due to the significant investment required in resource and training, many smaller biopharma companies often do not have a regulatory affairs department of their own. Therefore, its critical for sponsors to recognize the consultative benefit CDMOs bring to the table as an extension of their company to help fill in any regulatory knowledge gaps. This timely advice, integrated with early- and late-stage development, can enable a sponsor to adequately prepare, ensuring little or no delay when bringing its products to market.

See original here:
Making the Most of a CDMO Relationship - Genetic Engineering & Biotechnology News

Science writer, New Yorker contributor and author of the book Denialism Michael Specter joins Felix Salmon on the Slate Money podcast to break down the ongoing coronavirus crisis.

Specter explains how the virus spreads, potential food and medicine shortages it could cause and the possibility of developing immunity to infection. While the pandemic has shocked most of the world, Specter argues the only thing that should surprise anyone is the inept response of policy makers to the outbreak, particularly in the United States.

Specter also challenges some common misconceptions surrounding biotechnology, including the idea that GMOs are unnatural. Concerns about monoculture, the practice of growing a single crop like corn, on the other hand, are valid, Specter says. But that issue has nothing to do with genetic engineering. Its a problem that could be solved by a change in government policies: ending subsidies to corn and soybean growers. However, there are trade offs involved, and eliminating monoculture farms isnt the simple decision it seems.

Listen the to the original podcast

Read the original:
Podcast: Science writer Michael Specter on what you should know about the coronavirus, food security and GMOs - Genetic Literacy Project

Genetic engineering will allow the production of tomatoes and kiwis that are more tolerant to saline lands and will require less water. The initiative will also develop biostimulants directly applicable to plants to make them more tolerant to stress caused by drought and salinity .

Agriculture has been one of the activities hardest hit by climate change. Figures in this regard indicate that around 40% of the worlds land area corresponds to land affected by drought, a value that could increase to 50% between now and 2025.

One of the initial focuses of the project is to generate new varieties of tomatoes and kiwis using the CRISPR / Cas9 genetic engineering technique. In the case of tomato, the characteristics of Poncho Negro, a Chilean variety originating in the Azapa Valley that has high resistance to salinity and the effect of heavy metals, will be studied.

Components to improve tomato 7742 (seminis), the most widely produced and marketed variety in Chile, will also be investigated. Regarding kiwis, the aim will be to increase tolerance to salinity and drought of varieties used as rootstocks, to improve the productivity of Hayward commercial kiwi plants; the third most exported in Chile.

[Editors note: This article was published in Spanish and has been translated and edited for clarity.]

Read the original post

Read the original:
CRISPR gene editing could yield drought-tolerant tomatoes and kiwis that grow in salty soil - Genetic Literacy Project