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Impact Of Covid-19 on Nanomedicine Market 2020 Industry Challenges, Business Overview and Forecast Research Study 2026 – Crypto Daily

October 2nd, 2020 10:53 am

Manhattan, New York, Analytical Research Cognizance: TheNanomedicineMarketreport is based on the basis of product type, application and end-user during the truncated forecast period. The detailed study further offers a broad interpretation on the Nanomedicine market based on a systematic analysis of the market from a variety of reliable sources and thorough data points. Furthermore, the report sheds a light on the Global scale segmenting the market space across various districts, appropriate distribution channels, generated income and a generalized market space.

This intelligence and 2025 forecasts Nanomedicine industry report further exhibits a pattern of analyzing previous data sources gathered from reliable sources and set a precedented growth trajectory for the Nanomedicine market. The report also focuses on a comprehensive market revenue streams along with growth patterns, analytics focused on market trends, and the overall volume of the market.

Request Sample of Global Nanomedicine Market Report @https://www.arcognizance.com/enquiry-sample/923566

Finally, the report provides detailed profile and data information analysis of leading Augmented Reality Company.

This report covers leading companies associated in Nanomedicine Market @GE Healthcare, Johnson & Johnson, Mallinckrodt plc, Merck & Co. Inc., Nanosphere Inc., Pfizer Inc., Sigma-Tau Pharmaceuticals Inc., Smith & Nephew PLC, Stryker Corp, Teva Pharmaceutical Industries Ltd., UCB (Union chimique belge) S.A

Region Segmentation:North America (U.S., Canada, Mexico)Europe (Germany, U.K., France, Italy, Russia, Spain etc.)Asia-Pacific (China, India, Japan, Southeast Asia etc.)South America (Brazil, Argentina etc.)Middle East & Africa (Saudi Arabia, South Africa etc.)

On the basis of types, the Nanomedicine market is primarily split into:Regenerative Medicine, In-vitro & In-vivo Diagnostics, Vaccines, Drug Delivery

On the basis of applications, the market covers:Clinical Cardiology, Urology, Genetics, Orthopedics, Ophthalmology

Some of the major factors contributing to the growth of the global Nanomedicine market:

Nanomedicine Market Report Structure at a Glance:

Access Global Nanomedicine Market Report @https://www.arcognizance.com/report/global-nanomedicine-market-status-and-future-forecast-2015-2025

Table of Content:

Note:Our report does take into account the impact of corona virus pandemic and dedicates qualitative as well as quantitative sections of information within the report that emphasizes the impact of COVID-19.

As this pandemic is ongoing and leading to dynamic shifts in stocks and businesses worldwide, we take into account the current condition and forecast the market data taking into consideration the micro and macroeconomic factors that will be affected by the pandemic.

About us:Analytical Research Cognizance (ARC) is a trusted hub for research reports that critically renders accurate and statistical data for your business growth. Our extensive database of examined market reports places us amongst the best industry report firms. Our professionally equipped team further strengthens ARCs potential. ARC works with the mission of creating a platform where marketers can have access to informative, latest and well researched reports. To achieve this aim our experts tactically scrutinize every report that comes under their eye.

Contact Us:Ranjeet DengaleDirector SalesAnalytical Research Cognizance+1 (646) 403-4695, +91 90967 44448[emailprotected]

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Cristal Therapeutics announces a publication in ‘Chemical Science’ on CliCr technology platform, comprising a new class of superior copper free click…

October 2nd, 2020 10:53 am

For the optimal performance of CriPec nanomedicines, it is essential to be able to attach a broad range of small molecule active agents and large molecular entities, biologics, to CriPec nanoparticles.

The published research1reports the development of a convenient and versatile fast-reacting molecular entity for gluing very different compounds in a strain-promoted azide-alkyne cycloaddition click reaction to the nanoparticles, as well as a collection of linkers to attach the widely varying active small molecules and biologics. Next to the already demonstrated examples, many additional applications are foreseen such as the construction of antibody drug conjugates in aqueous environments with faster kinetics that is essential for these delicateconstructs.

CliCr is also used to generate virus mimicking nanoparticles. CriVac is a unique antigen carrier platform based on CriPec nanoparticles that, in contrast to viral vectors, do not convey a bystander immune response. CriPec particles' size resemble a virus and the desired numbers of antigen displayed on its surface are controlled via CliCr. CriVac mimics features of a live virus in a tailored manner to induce immunity safely, efficiently and solely to the displayed antigen, offering a prophylactic vaccination strategy which will be readily adaptable to different pathogenic treats.

The very attractive functionalisation possibilities, combined with its versatility, great reactivity and small size offer multiple opportunities for CliCrreagents to become the new standard for non-copper catalyzed click reactions in a multitude of applications.

Dr Cristianne Rijcken, CSO of Cristal Therapeutics, stated:

"This new versatile click reagent originates from an intense collaboration between industry and academic partners. For our nanomedicine applications, a fast, cleanly reacting and small click reagent is absolutely indispensable. These demands required the development of a new reagent, which will be highly attractive both for our proprietary applications and for the wider world of the biological, medical and material science applications. This is ground-breaking technology!"

In case you are interested to learn about the CliCr platform, please reach out to http://www.clicr.euor talk to us at the following virtual conferences

Reference

1. J. Weterings et al. TMTHSI, a superior 7-membered ring alkyne containing reagent for strain-promoted azidealkyne cycloaddition reactions, Chemical Science (2020)

https://pubs.rsc.org/en/content/articlehtml/2020/sc/d0sc03477k

About Cristal Therapeutics

Cristal Therapeutics is a phase 2 clinical-stage pharmaceutical company developing targeted nanomedicines for the treatment of cancer and other diseases with high unmet patient need and considerable commercial potential. The Company's product candidates are based on its proprietary CriPec polymeric nanoparticle technology platform, which enables the design of customized nanomedicines with superior therapeutic profiles. CriPec-based products have the potential to provide enhanced efficacy and reduced side effect profiles, thus offering improved disease treatment.

Find out more: http://www.cristaltherapeutics.com

For more information, please contact:

Cristal Therapeutics Jeroen van EgmondConsultant Business DevelopmentT: +31 6 272 048 89E: [emailprotected]

SOURCE Cristal Therapeutics

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UH Manoa scholars awarded ARCS Foundation grants for research – UH System Current News

October 2nd, 2020 10:53 am

Top for from left: Douglas Ellman, Branden Minei, Luke Campillo, Allexa Dow; Middle row from left: Marisa McDonald, Ashley McGuigan, John Runburg, Michael Honda, Priscilla Seabourn, Lauren Ching; Bottom row from left: Aileen Li, Brien Haun, Anamica Bedi de Silva, Trista McKenzie, Gagandeep Anand, Travis Berger

Sixteen University of Hawaii at Mnoa doctoral candidates have been awarded $5,000 Scholar Awards from the ARCS FoundationHonolulu Chapter. The 2020 awards were made in six UH Mnoa units.

ARCS Foundation works to advance science in America by providing unrestricted awards to outstanding U.S. graduate students in STEM fields. The chapter has provided more than $2 million to UH graduate students since 1974.

This award has not only provided monetary support for my research, but it shows that theres recognition for my work outside of my immediate sphere, and thats very meaningful, says ARCS Scholar Trista A. McKenzie.

McKenzie and her award donor are featured in the Honolulu Chapters first Meet-the-Scholar video, which was created after COVID-19 preempted the annual scholar presentations.

Douglas Ellman received the Bretzlaff Foundation Award in Engineering. He uses optimization and machine learning to study how distributed energy resources, such as solar batteries, electric vehicles and smart appliances, can be used to improve the operation of the electric grid.

Brenden M. Minei received the Frederick M. Kresser Award in Engineering. He developed a novel ceramic-based Nano-Paste that can be both 3D printed and molded to optimize and develop ceramic nanocomposite parts with armor as well as space structure and optical applications.

Read more about the College of Engineering scholars.

Luke Campillo received the Sarah Ann Martin Award in Natural Sciences. He sequences the DNA Hawaiian birds to study the impact of limited contact with other populations and competition for limited resources on speciation on island archipelagos.

Allexa Dow received the Ellen M. Koenig ARCS Award. She studies mechanisms employed by the deadly Mycobacterium tuberculosis pathogen to survive severe zinc depletion in the host, a necessary step for disease transmission.

Marisa S. McDonald received the Maybelle Roth ARCS Award in Conservation Biology. She is working to understand vision in larval mantis shrimp, focusing on ultraviolet vision function and use.

Ashley A. McGuigan received the ARCS Honolulu Award. She explores the connection between agroforest biodiversity and dietary nutrition in Fiji and the ways agroforestry helps people recover from major cyclone disturbances.

John Jack Runburg received the Sarah Ann Martin Award in Natural Sciences. He uses theoretical models and devises other methods to learn more about dark matter, the most common, but invisible, form of matter in the universe.

Read more about the College of Natural Sciences scholars.

Michael David Honda received the Kai Bowden ARCS Award. He is working to determine the mechanism of iron uptake in giant leucaena, which is used as a nutritious fodder-legume for farm animals.

Priscilla S. Seabourn received the Helen Jones Farrar Award. She uses DNA sequencing to characterize the microbiome and understand how environmental and ecological factors influence its diversity in Aedes albopictus mosquitoes, an insect that serves as a vector for Dengue and Chikungunya viruses, with an eye to improving strategies for disease prevention.

Read more about the CTAHR scholars.

Lauren Ching received the Koenig ARCS Award. She studies immunopathogenesis of Kawasaki disease, the leading cause of pediatric acquired heart disease in the developed world, to identify novel therapeutics that could ameliorate changes to coronary arteries.

Aileen S.W. Li received the Starbuck ARCS Award in Medicine. She uses in vitro model systems to understand the mechanisms of gastrulation, the foremost, crucial and sensitive stage of embryo development, and exposure to teratogens, agents that can cause birth defects.

Brien Haun received the Ellen M. Koenig ARCS Award. He is working to hack the immune system to uncover protective responses to emerging infectious viruses.

Read more about the JABSOM scholars.

Anamica Bedi de Silva received the George and Mona Elmore ARCS Award. She works on viral immunity in microbes, developing resistant strains of a single-cell algae for experimental evolution in the laboratory to determine if there are fitness costs to viral resistance.

Trista A. McKenzie received the Toby Lee ARCS Award in Earth Sciences. She studies groundwater pollution and discharge dynamics using a combination of field, lab and machine-learning approaches.

Read more about the SOEST scholars.

Gagandeep Deep Anand received the ARCS Honolulu Award. He is determining accurate distances to nearby galaxies using Hubble Space Telescope imaging to investigate the distribution of matter and evolution of galaxy groups and clusters.

Travis A. Berger received the Columbia Communications Award in Astronomy. He studies planet formation and evolution using stellar distances as measured by the Gaia space observatory of stars and exoplanets observed by the Kepler space telescope.

Read more about the IfA scholars.

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The Europe exosome diagnostic and therapeutic market is projected to reach US$ 12,524.24 thousand in 2019 to US$ 104,694.72 thousand by 2027 -…

October 2nd, 2020 10:53 am

New York, Oct. 01, 2020 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Europe Exosome Diagnostic and Therapeutic Market Forecast to 2027 - COVID-19 Impact and Regional Analysis By Application ; Product ; End User, and Country" - https://www.reportlinker.com/p05974359/?utm_source=GNW

Exosome is an emerging industry with a huge potential.Applications of exosomes are expanding rapidly in the areas of disease diagnosis and treatment as well as pharmaceuticals.

Exosomes are nanovesicles and act as a vehicle to deliver therapies to cells of the body.In the future, exosomes can be used as potential biomarkers and in the field of personalized medicine.

Interest in exosome research has increased dramatically in recent years, driving the growth of the exosome diagnostic and therapeutic market in the UK.New exosome therapeutics companies are rapidly entering the marketplace.

The investment flow has also increased to support such innovative therapeutic companies, further boosting the growth of the market. For example, in 2016, ReNeuron Group plc, a leading UK-based stem cell therapy development company, was awarded about US$ 2.6 million grant from Innovate UK to advance its emerging exosome nanomedicine platform.In terms of application, the diagnostics application segment accounted for a larger share of the Europe exosome diagnostic and therapeutic market. Its growth is attributed to an increasing adoption of exosome-based instruments and kits for diagnosis of chronic conditions. Additionally, exosome-based diagnostic products offer benefits such as accuracy, lower processing time, and better ergonomics; these are likely to drive the growth of diagnostic application segment in the Europe exosome diagnostic and therapeutic marketIn 2019, the instrument segment held a considerable share of the for exosome diagnostic and therapeutic market, by the product.This segment is also predicted to dominate the market by 2027 owing to higher demand for diagnostics instruments.

However, the software segment is anticipated to witness growth at a significant rate during the forecast period.A few major primary and secondary sources for the exosome diagnostic and therapeutic market included in the report are Instrument, US Food and Drug Administration, and World Health Organization, among others.Read the full report: https://www.reportlinker.com/p05974359/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

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The Europe exosome diagnostic and therapeutic market is projected to reach US$ 12,524.24 thousand in 2019 to US$ 104,694.72 thousand by 2027 -...

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Nanorobotics Market to Witness Huge Growth by 2024 | Bruker, JEOL, Thermo Fisher Scientific, Ginkgo Bioworks, Oxford Instruments – The Daily Chronicle

October 2nd, 2020 10:53 am

Global Nanorobotics Market report study covers the breakdown data with production, consumption, revenue and market share by regions, type and applications. Historical breakdown data from 2015 to 2019 and forecast to 2024

The comprehensive numerical analyses of Global NanoroboticsMarket Research Report 20202024 is a historical overview and in-depth study on the current & future market of the Nanorobotics industry. he report focuses on the historical and current market trends to predict the course of the global Nanorobotics market in the upcoming years. The report identifies opportunities, drivers, and major challenges faced by market players. The report discusses all major market aspects with expert opinion on current market status along with historic data. This market report is a detailed study on the growth, investment opportunities, market statistics, growing competition analysis, major key players, industry facts, important figures, sales, prices, revenues, gross margins, market shares, business strategies, top regions, demand, and developments. The research further provides par excellence futuristic estimations for various vital factors including market size, share, net profit, sales, revenue, and growth rate. The market competition by top manufacturers/players, with sales volume, price, revenue (Million USD) and market share for each manufacturer/player; the top players including market:Bruker, JEOL, Thermo Fisher Scientific, Ginkgo Bioworks, Oxford Instruments, EV Group, Imina Technologies, Toronto Nano Instrumentation, Klocke Nanotechnik, Kleindiek Nanotechnik. This report provides in-depth analysis of the Nanorobotics market and provides market size (US$ million) and compound annual growth rate (CAGR %) for the forecast period (20202024).

Request for Sample Report @https://www.indexmarketsresearch.com/report/global-nanorobotics-market/431987/#requestforsample

Global major manufacturers of the market are also assessed with their information such as company profiles, product picture and specification, capacity, production, price, cost, market trend, revenue, and contact data. The research provides details regarding each product like the cost breakup, import/export scheme, manufacturing volume, price, gross, growth ratio, investments, and contribution to the global Nanorobotics revenue. The facts and data are represented in the Nanorobotics Market report using diagrams, graphs, pie charts, and other pictorial representations. This enhances the visual representation and also helps in understanding the facts much better. We have provided a detailed study on the critical dynamics of the global Nanorobotics market, which include the market influence and market effect factors, drivers, challenges, restraints, trends, and prospects. Global Nanorobotics Industry Market Research Report is providing exclusive vital statistics, information, data, trends and competitive landscape details. The research study also includes other types of analysis such as qualitative and quantitative. The document also comprises of a detailed assessment of the regional scope of the market alongside its regulatory outlook. Additionally, the report provides with a detailed SWOT analysis while elaborating market driving factors. Furthermore, it sheds light on the comprehensive competitive landscape of the global market. Nanorobotics market report further offers a dashboard overview of leading companies encompassing their successful marketing strategies, market contribution, recent developments in both historic and present contexts.

The Nanorobotics market report includes the overall and comprehensive study of the Nanorobotics market with all its aspects influencing the growth of the market. This report is exhaustive quantitative analyses of the Nanorobotics industry and provides data for making strategies to increase the market growth and effectiveness. The Market report lists the most important competitors and provides the insights strategic industry Analysis of the key factors influencing the market. This report will help you to establish a landscape of industrial development and characteristics of the Nanorobotics market. The Global Nanorobotics market analysis is provided for the international markets including development trends, competitive landscape analysis, and key regions development status. It also provides statistical data on all the recent developments in the market. It also comprises a basic overview and revenue and strategic analysis under the company profile section. Nanorobotics market analysis is provided for the international markets including development trends, competitive landscape analysis, investment plan, business strategy, opportunity, and key regions development status. Development policies and plans are discussed as well as manufacturing processes and cost structures are also analyzed. This report also states import/export consumption, supply and demand Figures, price, cost, revenue and gross margins.

Regional Analysis:This section of the report contains detailed information on the market in different regions. Each region offers a different market size because each state has different government policies and other factors. The regions included in the report areNorth America (United States, Canada and Mexico), Europe (Germany, France, UK, Russia and Italy), Asia-Pacific (China, Japan, Korea, India, Southeast Asia and Australia), South America (Brazil, Argentina, Colombia), Middle East and Africa (Saudi Arabia, UAE, Egypt, Nigeria and SouthAfrica)Information about the different regions helps the reader to better understand the global Nanorobotics market.

Most important types of the market covered in this report are:Nanomanipulator, Bio-Nanorobotics, Magnetically Guided, Bacteria-Based

Most widely used downstream fields of market covered in this report are:Nanomedicine, Biomedical, Mechanical

Research objectives: The points that are discussed within the Nanorobotics Market report are the major market players that are involved in the market such as manufacturers, raw material suppliers, equipment suppliers, end users, traders, distributors and etc. Data and information by manufacturer, by region, by type, by application and etc, and custom research can be added according to specific requirements. The complete profile of the companies is mentioned. And the capacity, production, price, revenue, cost, gross, gross margin, sales volume, sales revenue, consumption, growth rate, import, export, supply, future strategies, and the technological developments that they are making are also included within the report. To analyze the Nanorobotics with respect to individual growth trends, future prospects, and their contribution to the total market. Focuses on the key global Nanorobotics manufacturers, to define, describe and analyze the sales volume, value, market share, market competition landscape, SWOT analysis and development plans in next few years. To project the consumption of Nanorobotics submarkets, with respect to key regions (along with their respective key countries). To strategically profile the key players and comprehensively analyze their growth strategies. The growth factors of the market are discussed in detail wherein the different end users of the market are explained in detail. The Nanorobotics market report contains the SWOT analysis of the market. Finally, the report contains the conclusion part where the opinions of the industrial experts are included.

Key Questions Answered: What is the size and CAGR of the global World Nanorobotics Market? Which are the leading segments of the global World Nanorobotics Market? What are the key driving factors of the most profitable regional market? What is the nature of competition in the global World Nanorobotics Market? How will the global Home Appliance market advance in the coming years? What are the main strategies adopted in the global World Nanorobotics Market? What are sales, revenue, and price analysis by types and applications of Nanorobotics market? What are sales, revenue, and price analysis by regions of Nanorobotics industry?

The Essential Content Covered in the Global Nanorobotics Market Report :* Top Key Company Profiles.* Main Business and Rival Information* SWOT Analysis and PESTEL Analysis* Production, Sales, Revenue, Price and Gross Margin* Market Share and Size

Read Detailed Index Report @https://www.indexmarketsresearch.com/report/global-nanorobotics-market/431987/

The Nanorobotics market report enumerates information about the industry in terms of market share, market size, revenue forecasts, and regional outlook. The report further illustrates competitive insights of key players in the business vertical followed by an overview of their diverse portfolios and growth strategies. This report is comprehensive numerical analyses of the Nanorobotics industry and provides data for making strategies to increase the market growth and success. The Report also estimates the market size, Price, Revenue, Gross Margin and Market Share, cost structure and growth rate for decision making. A detailed evaluation of the market by highlighting information on different aspects which include drivers, restraints, opportunities, threats, and global markets including progress trends, competitive landscape analysis, and key regions expansion status.

At last, This report investigates the Nanorobotics market in the global market, presents the latest business analysis including market scope, product situation, technology growth, environmental distribution, business situation, and chain structure. industrial. Nanorobotics Market Report Shares Important Data on Impact Factors, Advertising Drivers, Challenges, the report gives the inside and out examination of Nanorobotics Market took after by above components, which are useful for organizations or individual for development of their present business or the individuals who are hoping to enter in Nanorobotics industry.

Request customize If you wish to find more details of the report or want a Customization Please contacts us. You can get a detailed of the entire research here.

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Thalassemia Treatment Market projected to expand at a CAGR of 7.9% from 2018 to 2026 – The Daily Chronicle

September 30th, 2020 4:53 pm

Transparency Market Research (TMR)has published a new report titled, Thalassemia Treatment Market Global Industry Analysis, Size, Share, Growth, Trends, and Forecast, 20182026.According to the report, theglobal thalassemia treatment marketwas valued at US$ 842.0 Mn in 2017 and is projected to expand at a CAGR of 7.9% from 2018 to 2026. Increase in R&D investment by key players for developing new drugs for treating thalassemia and rise in demand for chelating therapy are anticipated to fuel the growth of the global market from 2018 to 2026. Asia Pacific and Middle East & Africa are expected to dominate the global market owing to increase in prevalence of thalassemia disorder and high adoption of chelation therapy & blood transfusion for treatment by doctors as well as patients. The market in Asia Pacific is projected to expand at the fastest CAGR during the forecast period. Growth of the market in the region is attributed to large base of private clinics and hospitals, rise in number of thalassemia population requiring chelation therapy services after spleen surgery, and surge in adoption of blood transfusion among patients. The thalassemia treatment market in Latin America is likely to expand at a moderate growth rate during the forecast period.

Request Brochure for Report https://www.transparencymarketresearch.com/sample/sample.php?flag=B&rep_id=44462

Value Added Features in Thalassemia Treatments to Propel Global Market

The global thalassemia treatment market is projected to be driven by value added features offered by various thalassemia drug manufacturing companies in order to streamline the day to day work flow and increase revenue. The thalassemia treatment provides limited range of features and benefits ranging from patient pain heeling remedies to treatment procedures. For instance, very less number of people go for the much beneficial chelation therapy. These features help physicians and nurses to streamline the chelation therapy required for patients to maintain their daily workflow efficiently and effectively. Key players offering thalassemia treatment are coming up with value added features such as bone marrow transplantation, stem cell regeneration, gene editing methodologies, and effective modality features used for drug manufacturing along with creating a prominent candidate molecule for drugs. These features can reduce the overall operating cost and improve the overall effectiveness and efficiency of treatment practices. Companies are focusing on the development of combined drug therapy in their system to effectively integrate chelating therapy or other treatment procedure at an affordable cost. These value added features save time for physicians and help improve thalassemia patient survival performance.

Request for Analysis of COVID19 Impact on Thalassemia Treatment Market https://www.transparencymarketresearch.com/sample/sample.php?flag=covid19&rep_id=44462

Chelation Therapy to be Highly Lucrative Segment

Traditionally, blood transfusion based on type of thalassemia treatment was the most commonly used procedure among thalassemia patients. This treatment type was associated with availability of donor and cost of treatment procedure. Moreover, chelation therapy based on thalassemia treatment are priced on perpetual license model and are expensive. Chelation therapy treatment enables patients to practice intensive therapy to treat acute iron overload leading to 90% recovery among thalassemia patients. These chelation therapy based treatments address specific challenges faced during the treatment procedure. The chelation therapy treatment facilitates benefits such as pain relief, and increase in motion of blood flow among patients.

Asia Pacific Presents Significant Opportunities

North America and Europe accounted for major share of the global thalassemia treatment market in 2017 and are likely to gain market shares by 2026. High rate of immigration from tropical regions, increasing health care budgets by governments, and government initiatives to promote thalassemia treatment technique contributed to the leading share of these regions. Asia Pacific is projected to be the most attractive market for thalassemia treatment, with highest attractiveness index. The market in Asia Pacific is expected to expand at a high CAGR of 9% during the forecast period due to large number of thalassemia patients opting for chelation therapy in developing countries such as India and China. Well-established health care facilities, medical tourism for treatment of thalassemia, and high adoption of blood transfusion safety technique in countries such as Turkey and GCC Countries are likely to drive the market in Middle East & Africa. The market in Latin America is poised to expand at a moderate growth rate during the forecast period.

Buy Thalassemia Treatment Market Report https://www.transparencymarketresearch.com/checkout.php?rep_id=44462&ltype=S

Trend of R&D among Leading Players to Increase Geographic Presence

The report also provides profiles of leading players operating in the global thalassemia treatment market. bluebird bio, Inc., Acceleron Pharma, Inc., Novartis AG, Celgene Corporation, and Shire plc (Takeda Pharmaceuticals) are the leading players operating in the global market. Companies operating in the thalassemia treatment market aim to increase geographic presence and research & development through strategic acquisitions and collaborations with leading players in respective domains and region. In December 2017, Shire plc committed to pay approximately US$ 1,409.9 Mn to contract vendors for administering and executing clinical trials. Other prominent players operating in the global thalassemia treatment include Incyte Corporation, Kiadis Pharma, Gamida Cell, Celgene Corporation, and Bellicum Pharmaceuticals.

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Thalassemia Treatment Market projected to expand at a CAGR of 7.9% from 2018 to 2026 - The Daily Chronicle

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Mild to severe: Immune system holds clues to virus reaction – ABC News

September 30th, 2020 4:51 pm

One of COVID-19's scariest mysteries is why some people are mildly ill or have no symptoms and others rapidly die and scientists are starting to unravel why.

An international team of researchers found that in some people with severe COVID-19, the body goes rogue and attacks one of its own key immune defenses instead of fighting the coronavirus. Most were men, helping to explain why the virus is hitting men harder than women.

And separate research suggests that children fare better than adults thanks to robust first responder immune cells that wane with age.

They're the latest in a list of studies uncovering multiple features of the immune system's intricate cascade that can tip the scales between a good or bad outcome. Next up: Figuring out if all these new clues might offer much-needed ways to intervene.

We have the knowledge and capability of really boosting many aspects of the immune system. But we need to not use the sledge hammer, cautioned Dr. Betsy Herold of New York's Albert Einstein College of Medicine, who co-authored the child study.

Adding to the complexity, people's wildly varying reactions also reflect other factors, such as how healthy they were to begin with and how much of the virus the dose" they were exposed to.

Infection and what happens after infection is a very dynamic thing, said Alessandro Sette, a researcher at the La Jolla Institute for Immunology in San Diego, who is studying yet another piece of the immune response.

IMMUNE PRIMER

There are two main arms of the immune system. Innate immunity is the bodys first line of defense. As soon as the body detects a foreign intruder, key molecules, such as interferons and inflammation-causing cytokines, launch a wide-ranging attack.

Innate immune cells also alert the slower-acting adaptive arm of the immune system, the germ-specific sharpshooters, to gear up. B cells start producing virus-fighting antibodies, the proteins getting so much attention in the vaccine hunt.

But antibodies aren't the whole story. Adaptive immunity's many other ingredients include killer T cells that destroy virus-infected cells and memory T and B cells that remember an infection so they spring into action quicker if they encounter that germ again.

A MISSING PIECE

Usually when a virus invades a cell, proteins called Type I interferons spring into action, defending the cell by interfering with viral growth. But new research shows those crucial molecules were essentially absent in a subset of people with severe COVID-19.

An international project uncovered two reasons. In blood from nearly 1,000 severe COVID-19 patients, researchers found 1 in 10 had what are called auto-antibodies antibodies that mistakenly attack those needed virus fighters. Especially surprising, autoimmune disorders tend to be more common in women but 95% of these COVID-19 patients were men.

The researchers didn't find the damaging molecules in patients with mild or asymptomatic COVID-19.

In another 660 severely ill patients, the same team found 3.5% had gene mutations that didn't produce Type I interferons.

Each of those silent vulnerabilities was enough to tip the balance in favor of the virus early on, said Dr. Jean-Laurent Casanova, an infectious disease geneticist at Rockefeller University in New York, who co-leads the COVID Human Genetic Effort.

Certain interferons are used as medicines and are under study as a possible COVID-19 treatment; the auto-antibody discovery adds another factor to consider.

KIDS' IMMUNITY REVS FAST

It's not clear why children appear less at risk from COVID-19. But occasionally they're sick enough for hospitalization, giving Herold's team the opportunity to compare 60 adults and 65 children and teens at New Yorks Montefiore Health System.

The children produced much higher levels of certain cytokines that are among the innate immune system's first responders. When the immune system's next stage kicked in, both adults and children made antibodies targeting the coronavirus. Here's the rub: The adults' adaptive immune response was more the type that can trigger an inflammatory overreaction.

The findings suggest kids' early robust reaction lets their immune system get ahead of the virus, making an overreaction less likely "and that's protecting them, Herold said.

ANY PREEXISTING IMMUNITY?

The coronavirus that causes COVID-19 is new to humans. But Sette's team studied blood samples that were stored in freezers before the pandemic and found some harbored memory T cells that recognized a tiny portion of the new virus in laboratory tests.

You can actually tell that this is an experienced T cell. This has seen combat before, Sette said. Researchers in Germany, Britain and other countries have made similar findings.

The new coronavirus has cousins that cause as many as 30% of common colds, so researchers believe those T cells could be remnants from past colds.

But despite the speculation, we don't know yet that having those T cells makes any difference in who gets seriously sick with COVID-19, noted Rory de Vries, co-author of a study in the Netherlands that also found such T cells in old blood.

All these findings beg for a deeper understanding of the myriad ways some people can be more susceptible than others.

We need to look quite broadly and not jump into premature conclusions about any one particular facet of the immune system, said Stanford University immunologist Bali Pulendran. He also has found some innate immune cells in a state of hibernation in seriously ill adults and next is looking for differences before and after people get sick.

But, it's not just all about the immune system, cautioned Dr. Anita McElroy, a viral immunity expert at the University of Pittsburgh Medical Center whos closely watching the research. A way to tell in advance who's most at risk? Were a long, long way from that.

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institutes Department of Science Education. The AP is solely responsible for all content.

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The immune system: How to boost it and lower your immune age – New Scientist News

September 30th, 2020 4:51 pm

Your immune system stands between you and deadly infections. But as you get older so does your immune age, making you more susceptible to disease. Fortunately, we are discovering plenty of things you can do to turn back the clock and stay healthy. In this episode of our video series Science with Sam, find out how your immune system works and how you can give it a boost.

Tune in every week toyoutube.com/newscientistfor a new episode, or check back tonewscientist.com

One of the most important things standing between you and a deadly infection is your immune system the intricate, biological defence mechanism that protects your body from harmful invaders. And theres a lot we can do to give our immune system a helping hand.

Your immune system is made up of two divisions: the innate immune system and the adaptive immune system, each with its own battalion of specialist cells and defensive weapons.

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The innate immune system is the first line of defence. Its made up of cells like the scary-sounding macrophage, and the less scary-sounding neutrophil. These general-purpose guards patrol the bloodstream on the lookout for anything that shouldnt be there. When they detect an intruder, they neutralise the threat by engulfing it like Pac-Man, spraying it with deadly chemicals or suicidally expelling their DNA and throwing it around the invader like a net.

Then theres the adaptive immune system, which you can think of as the immune systems special forces, elite agents trained to fight specific pathogens. Unlike the innate system, which can attack any invading cell or virus, these cells are only effective against one enemy, and they must be trained to fight them first.

B cells fight bacteria and viruses by making Y-shaped proteins called antibodies that neutralise an invader or tag it for attack by other parts of the immune system.

Then there are T cells. These coordinate and carry out attacks on infected cells. Helper T Cells call in reinforcements by sending out chemical messages known as cytokines. Killer T-Cells are the front line soldiers, trained, as the name suggests, to destroy the enemy.

When we encounter a disease for the first time, it takes a while for the adaptive immune system to learn how to fight it. But once its up and running, it creates a memory, allowing a fast and brutal response to future infections often neutralising it before you even notice. This is the premise of vaccines and the reason why you only get diseases like chicken pox once.

If you want to know more about vaccines, theres a video all about them, just hit the link at the end of this video. Better yet, subscribe to New Scientist today and get 20 per cent off if you enter the code SAM20 at checkout.

Your immune system works so well that, most of the time, you wont even notice it. But it weakens as you get older, making you more susceptible to infection. Thats a key reason why people over the age of 70 are most vulnerable to diseases like covid-19, or even the flu.

This decline happens to all of us, but it can be accelerated by lifestyle factors like smoking and inactivity. Obesity is also linked to a faster decline in immune potency.

All of which means that, although the strength of your immune system is linked to your age, a 40-year-old can have the immune system of a 60-year-old. Or on the flipside, a healthy 60-year-old may have the immune system of a 40-year-old.

Scientists have recently developed ways to measure your immune age. Fortunately, it turns out your immune age can go down as well as up. And there are some simple ways to turn back the clock on your immune system.

As we get older, some of our immune cells start to misbehave. Take neutrophils, those early responder cells. As they age, they get worse at hunting down intruders, blundering through your tissues, causing damage.

The root of the problem is an overactive enzyme involved in their sense of direction. Dialling down that enzyme rejuvenates the neutrophils so they know where theyre going. And theres a simple, drug-free way to do it: exercise.

One study in older adults showed that those who got 10,000 steps a day on average had neutrophils as good as a young adult.

Exercise also has benefits for your T cells. Before they are released onto active duty, T-cells mature in a little-known organ called the thymus gland in your chest. The thymus degenerates over time, resulting in a drop-off in the number of T cells.

Physical activity has a huge effect on the rate of this degeneration. A study found that amateur cyclists aged between 55 and 79 had youthful thymus glands and their T-cell counts were similar to those of much younger people.

Another key factor in your immune age is your gut bacteria. There is good evidence that poor gut health is a cause of premature ageing and that a healthy microbiome can reduce your immune age. Eating a healthy, varied diet rich in fibre, plant matter and fermented foods can help maintain a healthy community of gut microbes.

Your body has a highly evolved, intricate defence system thats effective at keeping you well, but only if you look after it.

I dont know about you but Ive been a bit less active of late, so Im considering this something of a wake-up call.

Looking after your immune system is a no-brainer, and its as easy as a walk in the park.

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Strong activation of anti-bacterial cells of immune system linked to severe Covid-19: Study – Hindustan Times

September 30th, 2020 4:51 pm

A type of the immune systems T cells known to fight against bacterial infections is strongly activated in people with moderate to severe Covid-19, according to a study which provides a better understanding of how the body responds to the novel coronavirus infection.

Researchers, including those from the Karolinska Institutet in Sweden, noted that this component of the immune system called MAIT cells make up about one to five percent of T cells in the blood of healthy people, and are primarily important for controlling bacteria, but can also be recruited to fight some viral infections.

They explained that T cells are a type of white blood cells that are specialised in recognizing infected cells, and are an essential part of the immune system. In the current study, published in the journal Science Immunology, the scientists assessed the role played by MAIT cells in Covid-19 disease.

They examined the presence and character of MAIT cells in blood samples from 24 patients admitted to Karolinska University Hospital with moderate to severe Covid-19 disease, and compared these with blood samples from 14 healthy controls and 45 individuals who had recovered from Covid-19. Four of the patients died in the hospital, the study noted.

To find potential treatments against Covid-19, it is important to understand in detail how our immune system reacts, and in some cases, perhaps contribute to worsening the disease, said Johan Sandberg, a co-author of the study at Karolinska Institutet.

According to the study, the number of MAIT cells in the blood decline sharply in patients with moderate or severe Covid-19, and the remaining cells in circulation are highly activated.

Based on these results, the scientists suggested that the MAIT cells are engaged in the immune response against the novel coronavirus SARS-CoV-2. This pattern of reduced number and activation in the blood is stronger for MAIT cells than for other T cells, they said. The study also noted that pro-inflammatory MAIT cells accumulated in the airways of Covid-19 patients to a larger degree than in healthy people.

Taken together, these analyses indicate that the reduced number of MAIT cells in the blood of Covid-19 patients is at least partly due increased accumulation in the airways, Sandberg said.

The scientists added that the number of MAIT cells in the blood of convalescent Covid-19 patients recovered at least partially in the weeks after disease, which can be important for managing bacterial infections in individuals who have had Covid-19. They said the MAIT cells tended to be extremely activated in the patients who died.

The findings of our study show that the MAIT cells are highly engaged in the immunological response against Covid-19, Sandberg said. The scientists believe the characteristics of MAIT cells make them engaged early on in both the systemic immune response, and in the local immune response in the airways to which they are recruited from the blood by inflammatory signals.

There, they are likely to contribute to the fast, innate immune response against the virus. In some people with Covid-19, the activation of MAIT cells becomes excessive and this correlates with severe disease, Sandberg added.

(This story has been published from a wire agency feed without modifications to the text.)

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ETHZ-led group shows that nervous system directly influences immune system – Optics.org

September 30th, 2020 4:51 pm

29Sep2020

Optogenetics researchers in Switzerland and US have optically stimulated nerve fibers in living mice.

Through this process, they have demonstrated that the nervous system has a direct influence on the immune system.

Over the past ten years, a new method has literally shed more light on the brain: optogenetics allows scientists to dstimulate genetically-modified nerve cells and investigate their functioning within the complex network inside the skull. This technique represents a revolution in neuroscience, say the Swiss-US team, but to date, it could only be applied to study the central nervous system, and not the peripheral nervous system.

A team of electrical engineers led by Qiuting Huang, a professor at the Institute for Integrated Systems at ETH Zurich, have developed a system that connects implantable LEDs with a tiny device on the subjects head which can be controlled from a tablet via Bluetooth. They have stimulated, with great precision, nerve fibers in the bodies of freely-moving mice, as the scientists report in Nature Biotechnology.

Our goal was to develop an integrated platform as small as possible. Together, the chip, the battery and the antenna for wireless signal transmission weigh less than one gram and occupy less than one cubic centimetre, explained Huang.

While the chip technology enables high integration density of electronic circuits, there are limits to miniaturization, particularly with batteries; the smaller the volume, the greater the energy density. This, in turn, increases the risk that batteries might ignite.

The team originally intended to develop this platform for a project to measure oxygen saturation and blood pressure, but right from the outset of the design phase, they endeavored to ensure the widest possible application for the chip.

Because our system is programmable, we were able to take the electronic circuits that we had been intending to use to measure oxygen saturation in blood and re-purpose them to control the implanted light emitting diodes, said contributing scientist Philipp Schnle.

The group has been collaborating with Stphanie Lacours group at EPFL for five years. Our sophisticated electronics and their soft bioelectronic sensors were made for each other, said Huang. Advances in material sciences and electronics build on each other and interconnect with each other. Together, we have developed an approach that allows us to stimulate a specific nerve fiber in the body of the mouse at precise points in time, added Schnle.

At Harvard Medical School, a research group led by Clifford Woolf wrapped the implants around the sciatic nerve. Without damaging the nerve, over several days, they managed to repeatedly use blue light flashes to activate specific nerve cells known as the nociceptors, which specialize in the transmission of pain signals.

To their surprise, the researchers discovered that repeated optical stimulation of these nociceptors produced a slight reddening in one of the mouses hind paws, a clear sign of inflammation.

Scientists had previously assumed that pain and inflammation were two different processes that arose independently. But now we have been able to prove conclusively that the neurons responsible for pain sensations can also generate an inflammatory immune response, said Woolf. As the researchers explain in the Nature Biotechnology article, these results may potentially point the way to new approaches in such areas as the treatment of chronic pain, or persistent inflammation.

Huang believes that electrical engineering will play an increasingly important role in human health in the future. He highlights the term electroceuticals a combination of electronics and pharmaceuticals which is already being discussed among experts.

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Agios helps identify genes that allow cancer to escape the immune system – FierceBiotech

September 30th, 2020 4:51 pm

Despite the availability of multiple FDA-approved immunotherapies that leverage the bodys immune system to fight cancer, only a fraction of cancer patients are benefiting. That's because cancer cells are cunning. They develop strategies to avoid being targeted and destroyed by immune cells.

To understand the genetic drivers behind the ability of cancer cells to evade the immune system, scientists at the University of Toronto, in collaboration with Agios Pharmaceuticals, used CRISPR to screen six genetically diverse mouse cancer cell lines. They found that genes involved in autophagya process where cells recycle damaged components to regenerate themselveswere key for immune evasion.

The researchers suggested that their findings, published in Nature, open up new venues for the development of immunotherapies that could be effective for largepatient populations across several different tumor types.

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Its very important to understand at the molecular level how cancer develops resistance to immunotherapies in order to make them more broadly available, saidUniversity of Toronto professor Jason Moffat, Ph.D., the studys corresponding author, in a statement.

Moffat and colleagues used CRISPR to screen cancer cells that were cultured in the presence or absence of preactivated killer T cellsimmune cells with a natural ability to hunt and kill cancer. They identified 182 genes that, when deleted, increased either the sensitivity or theresistance of cancer cells to T cells. They called them core cancer-intrinsic cytotoxic T lymphocyte-evasion genes, becauseevery one of them was present across at least three of the six cells lines that the team screened.

The core set of genes included several genes that were known to affect signaling of interferon gamma, a cytokine thats critical to an array of immune responses and that serves as a master communicator with several types of immune cells. Three negative regulators of the interferon-gamma responseSocs1, Ptpn2 and Adaralso emerged as immune-evasion genes.

Several genes identified were related to autophagy. Among the top hits was the Fitm2 gene, which is required for normal fat storage in adipose tissue in mice but was not previously associated with interferon-gamma signaling.

RELATED:New strategies for improving pancreatic cancer treatments

In two mouse models of renal cell carcinoma and melanoma, cancer cells with deleted Fitm2 showed increased cell death after treatment with interferon gamma compared with control cells, the team reported.

Surprisingly, the researchers also found that deleting certain autophagy genes in pairs could make the cells resist T-cell killing. For example, cells that lacked both Atg12 and Atg5 were strongly resistant to the killing effects of T cells as compared with single-mutant cells. This means that if a tumor already harbors a mutation in one autophagy gene, an immunotherapy that targets another autophagy gene could make the disease worse, the researchers explained.

Other oncology researchers are also focusing on the autophagy. A team from the University of Cincinnati, for example, found that mutations in mitochondrial complex I could prevent the autophagy thats triggered by mTOR inhibitors. And researchers at the University of North Carolina reported that targeting the KRAS mutation in pancreatic cancer with an MEK inhibitor made cancer cells more dependent on autophagy for survival. They blocked the process with the anti-malaria drug hydroxychloroquine.

The University of Toronto-led team believes its list of 182 core immune-evasion genes may inform efforts to develop novel cancer immunotherapies. The scientists stressed the need to explorehow combined genetic interactions may alter cancers immune-evasion activity. While simultaneous control of certain genetic features may sensitize cancer cells to immunotherapy, it could make the disease worse in others, they warned.

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Genetic Engineering Drug Market 2020 | What Is The Estimated Market Size In The Upcoming Years? – The Daily Chronicle

September 30th, 2020 4:50 pm

The Global Marketers provides you regional research analysis on Genetic Engineering Drug Market and forecast to 2026. The global Genetic Engineering Drug Market report comprises a valuable bunch of information that enlightens the most imperative sectors of the Genetic Engineering Drug market. The global Genetic Engineering Drug market report provides information regarding all the aspects associated with the market, which includes reviews of the final product, and the key factors influencing or hampering the market growth.

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Main players in the Genetic Engineering Drug Market:

GeneScience Pharmaceuticals Co., LtdBeijing SL Pharmaceutical Co., LtdBiotech Pharmaceutical Co., LtdShenzhen Neptunus Interlong Bio-Technique Co., LtdJiangsu Sihuan Bioengineering Co., LtdTonghua Dongbao Pharmaceutical Co., LtdAnhui Anke Biotechnology (Group) Co., Ltd3SBio Inc.Shanghai Lansheng Guojian Pharmaceutical Co., Ltd

Some of the geographic regions examined in the overall Genetic Engineering Drug Market are:

In addition, the global Genetic Engineering Drug market report delivers brief information about federal regulations and policies that may ultimately affect market growth as well as the financial state. The situation of the global market at the global and regional levels is also described in the global Genetic Engineering Drug market report through geographical segmentation. The Genetic Engineering Drug report introduces speculation attainability evaluation, a task SWOT investigation, and venture yield evaluation.

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Global Genetic Engineering Drug Market Segmentation:

On the Basis of The Application:

30 Years Old30 Years Old-60 Years Old60 Years Old

On the Basis of Type:

Monoclonal AntibodyRecombinant Human ErythropoietinRecombinant Human InterferonRecombinant Human Growth HormoneRecombinant Human Insulin

Moreover, the report comprises the main developments made in the Genetic Engineering Drug market. Porters five force analysis is used to conclude the competition in the Genetic Engineering Drug market along with new entrants and their strategies & tactics. The report involves the value chain analysis which denotes workflow in the Genetic Engineering Drug market. Also, the market has been classified on the basis of category, processes, end-use industry, and region. On the basis of geography, the report Genetic Engineering Drug the market.

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The Genetic Engineering Drug Market research report presents a comprehensive analysis of the market and contains attentive insights, facts, past data, and statistical support, and industry-validated market data. It furthermore contains projections applying a suitable set of assumptions and methodologies. The research Genetic Engineering Drug report provides examination and information according to market segments such as geographies, applications, and industry by considering major players.

Key questions answered in this report

Highlights of the TOC of the Genetic Engineering Drug Report:

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Orphan Drug Exclusivity for CRISPR/Cas-Based Therapeutics – JD Supra

September 30th, 2020 4:50 pm

The prospect of genetic engineering using CRISPR (clustered regularly interspaced short palindromic repeats) and CRISPR-associated nucleases (Cas) has long been hailed as a revolutionary development in medicine.

This technology is rapidly advancing, and several CRISPR/Cas-based drugs have entered clinical trials over the past several years. One kind of product in clinical trials is CRISPR-modified cells, such as CTX001 (CRISPR-Cas9-modified autologous hematopoietic stem cells), currently under study for the treatment of b-thalassemia and severe sickle cell anemia. Another CRISPR-based product, AGN-151587, is injected into the eye with the goal of eliminating a genetic mutation in patients with Leber congenital amaurosis 10, a leading cause of childhood blindness. In parallel, others are working to harness the CRISPR/Cas system to develop drugs for rare diseases, including bespoke therapies tailored to an individual patients needs.

Given CRISPR/Cas-based drugs potential to treat rare diseases, issues relating to orphan drug exclusivity will arise as these products are developed. In May 2020, for example, CTX001 received an orphan drug designation for transfusion-dependent b-thalassemia.

In January 2020, the FDA provided draft guidance regarding orphan drug exclusivity for gene therapy products, which includes CRISPR/Cas gene editing (Draft Guidance). This guidance focuses on the analysis of whether two gene therapy products are the same under the Orphan Drug Act. Although informative, the limited scope of the Draft Guidance invites more questions than it answers.

Same Drugs Under the Orphan Drug Act

Obtaining orphan drug exclusivity involves a two-step process. First, a sponsor requests designation of a drug for a particular rare disease or condition. See 21 C.F.R. 316.20. If this drug is the same drug as a drug already approved to treat the same rare disease or condition, the sponsor must provide a plausible hypothesis that the new drug is clinically superior to the previously-approved drug. Id. Whether two drugs are the same depends on consideration of structural features relevant to that type of drug. See id. 316.3(b)(14).

If the new drug later obtains marketing approval for a use or indication within the rare disease or condition for which it received orphan drug designation, the FDA will determine if the drug is eligible for orphan drug exclusivity. See 21 C.F.R. 316.31(a). In this situation, to receive exclusivity, the sponsor of the new drug must show that its drug is clinically superior to the same previously-approved drug for the same rare disease or condition. See id. 316.34(c). A clinical superiority determination is based on the new drugs greater efficacy, greater safety, or a major contribution to patient care. See id. 316.3(b)(3).

Highlights from Draft FDA Guidance

To determine whether one gene therapy product is the same as another, per 316.3(b)(14)(ii), the FDA will evaluate the principal molecular structural features of the two products, particularly transgenes (e.g., transgenes that encode different enzymes for treatment of the same rare disease) and vectors. For example:

Additionally, [w]hen applicable, the FDA generally intends to consider additional features of the final gene therapy product, such as regulatory elements or, in the case of genetically-modified cells, the type of cell that is transduced. It generally intends to consider requests for designation and exclusivity of gene therapy products to evaluate whether such additional features may also be considered to be principal molecular structural features.

Implications for CRISPR/Cas Therapy Exclusivity

The Draft Guidance helps answer certain high-level questions relating to whether two gene therapy products would be considered the same under the Orphan Drug Act. As various stakeholders have recognized, however, it is short on the details that meaningfully aid the process of drug research and development.

It is clear from the Draft Guidance that a new product can be considered the same as a previously-approved product even if the two products are not perfectly identical, but the guidance does not explain what would constitute a minor difference between such products, or what the scope of additional features would be.

For example, the Draft Guidance does not clarify what makes two transgenes the same. Nor does it cite to prior guidance or regulations that may answer this question. The question is significant because Cas nucleases and other parts of the CRISPR/Cas system may be modified in various ways. To address whether these modifications bar a finding of same-ness, the FDA could potentially import the kinds of considerations that govern same-ness of other kinds of large-molecule products, such as polynucleotide drugs or closely related, complex partly definable drugs with similar therapeutic intent (e.g., viral vaccines). See 21 C.F.R. 316.3(b)(14)(ii)(C), (D). However, this is not clear from the Draft Guidance.

The Draft Guidance also does not explain what will factor into the case-by-case basis assessment of whether viral vectors from the same viral class are the same. In the case of AAV2 and AAV5the two viruses identified in the guidanceresearchers have found that these viruses differ with respect to sequence analysis, tissue tropism, and heparin sensitivity. It is not clear from the guidance, however, whether a plausible hypothesis of clinical superiority will be required to seek orphan drug designation for a drug based on AAV2 if the previously-approved drug expresses the same transgene(s) but is based on AAV5.

It would be beneficial to sponsors and other stakeholders if these aspects of gene therapy drugs sameness are clarified further before they invest significant resources into the design and development of these therapeutics.

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Inventing the future for humankind | Community Perspectives – Fairbanks Daily News-Miner

September 30th, 2020 4:50 pm

Back in the halcyon days, when I somehow got paid for messing with the minds of the impressionable youth of UAF, I liked to ask said minds to project themselves back in time 400 years, to take a look around and report back what, if anything, they noticed different between those times (counting back from now, for example, to the Lords Year 1620. (James I was King, if that helps) and our own times: changes in musical tastes, ethics, physics, theology or attitudes regarding leprosy, for instance.

1620 CE was earlier than heart transplants, genetic engineering and baseball. It was before George Washington and water-seal toilets. Oxygen wouldnt be invented until the mid-1700s (Really: no Periodic Table of Elements, no radioactivity). The Holy Inquisition was in practice: pious religious officials were still torturing heretics and burning witches. It was before abortion rights. Autochthonous peoples in many parts of the world had not been introduced to the blessings of European economics, religion and warfare. It was before Facebook.

Things had changed in the last 400 years. Bigly. My students always got that answer right.

Then Id ask them to project themselves 400 years into the future, to the early 25th Century, say, to look around, to report back. I asked them to pay particular attention to the way our descendants in 2420 look back on our (presumably long-obsolete) ways of doing things: our medicine, say, or our governmental systems, or our responses to global hunger, overpopulation, pollution.

This was a harder task. The problem with prognostication is that we normal people are not particularly good at it, being annoyingly set in our ways. This is not to say that we cant make predictions, but even deeply considered and finely calibrated events such as space launches, brain surgery, or steering an oil tanker around Bligh Reef occasionally go awry. Some events, like nuclear meltdowns or worldwide pandemics, can present unanticipated difficulties.

I asked my students to avoid fantasies like self-aware computers, two-way wrist radios or honest politicians. I was hoping for revolutionary ways of perceiving the world, something on the order of the atalatl, General Relativity or Akira Kurosawa. I was angling for new stuff: examples of true scientific, artistic or musical invention.

My students always protested. Were on to you, old man, you you English teacher! Youve been harping all semester about how we mortals really cant see into the future, that we make up the future with our words. Now you want us to think something no one has ever thought before!

Thats exactly what I wanted them to do, of course. To be fair, really new ideas are not particularly common. It took humans millennia to come up with the atlatl (c.20,000 BCE), even longer to invent the calculus (c.1665 CE) or germ theory (c.1840). But without inventive ways of looking at the world, humanity might still believe that malaria is caused by bad air, that light travels across a medium called luminiferous ether, or that things burn because they contain phlogiston.

Theres been much talk lately of returning to normal, but I wonder if thats really what we want. I wonder if normal isnt what got us into our present public health and economic crises. I think for a lot of people in our community normal is worrying about buying groceries, paying the rent, health care, personal safety.

In this Year of Our Trump and the Corona pandemic (known also to certain elderly cynics as the beer virus or the sniffles) the question for my students would be, Given that we really cant see into the future and given that our current pandemic is unlikely to be our last, whats our best strategy for the survival of Our People (defined however you like) for the next seven generations or so?

Id hope for some inventive thinking along the lines of how to take care of every person on Earth in honest and practical ways. Emphasizing that we have plenty to be humble be about when predicting the future, Id ask them to come up with ideas never tried before. Id suggest that food, shelter and health care need never to be money-dependent, for example. Id ask our youth for creative ways of feeding people, sheltering people, caring for people all people on this, our planetary spaceship.

Id invite them to approach the task with an honest and generous spirit.

Lynn Basham lives in Fairbanks. He taught atthe University of Alaska Fairbanks as an instructor, mostly in the English Department, for about 20 years and retired about10 years ago.

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Family seeks answers, finds hope after daughters diagnosed with rare genetic condition – Steamboat Pilot and Today

September 30th, 2020 4:50 pm

STEAMBOAT SPRINGS You can hear the love in Mariah Gillaspies voice as she talks about her daughters Emma and Abby, who suffer from a rare genetic disease that causes seizures and development issues.

Emma, shes our oldest, and shell be 4 in October, Mariah said. Shes our calm, sweet little child. She has these little coos that sound like a dove. She really enjoys music, and she loves being around other kiddos her age.

Abby is our younger daughter, and shell be 2 in October, and she is our feisty little thing, Mariah continued. So, she lets you know when shes happy; she lets you know when shes not happy.

There is no question the two girls, the only two people in the world believed to have this disease, are surrounded by the love they get from Mariah and their dad Mark.

Mark grew up in Steamboat Springs and graduated from high school here in 2001. The couple now live in Centennial, but Marks parents, Jeanne and Joe Gillaspie, still live in Steamboat as does Marks older brother.

Four years ago, Mark and Mariah were overwhelmed with joy as they welcomed their first child Emma to the world, but when she was three months old, the couple started to notice she was having some strange movements, and when she started having episodes where she would hold her breath until she would turn pale, the couple took her to the doctor.

The doctor initially thought it was reflux, but when Emma stopped breathing in the doctors office, she was rushed to Childrens Hospital of Colorado for more evaluation and tests.

Throughout all this, I was convinced everything was going to be OK, Mariah said. It never crossed my mind that something was seriously wrong, and I had never considered that these were seizures.

Eventually, Emma was diagnosed with infantile spasms, which Mariah said didnt look serious on the outside but were damaging Emmas brain and impacting her development from the inside. Emma started treatment immediately, and the family was encouraged with the results. But then there was a relapse and a new medication, and then another relapse and another new medication.

Mariah said each new medicine came with a longer list of side effects, and Emmas immune system suffered. She had a bout with pneumonia that left her in the hospital for two months.

Through it all, the Gillaspies continued to search for answers.

We did a whole slew of genetic testing, and it came back inconclusive, Mariah said. They found absolutely nothing that could be the cause of her disease, and they told us this is probably some completely random condition that was caused by something that happened in utero.

They also told the Gillaspies that Emmas condition was rare, and there was less than a 3% chance of it happening again. So after extensive genetic testing, they decided to have a second child.

When Abby arrived two years later, they were thrilled, but at about six weeks, they noticed their youngest daughter was displaying the same movements that Emma had shown prior to her diagnosis. So it was back to the doctors, and it was confirmed through genetic testing that Abby and Emma shared the same mutated gene THAP12.

After discovering their daughters were suffering from the same condition, the family embarked on a grassroots effort to drive research about the rare genetic disease, which led to the creation of a foundation, Lightning and Love, a name that was chosen because the family believes lightning struck their family twice in the form of two daughters with the same rare disease.

The doctors would say, Im sorry, theres nothing we can do. We have to wait for science to catch up,' Mariah said. Every doctor that weve encountered has really been amazing and done their very best for us. Its just unfortunate science hasnt caught up to the girls, yet. Thats kind of, whereas parents, were passionate enough to move science along a little faster.

The nonprofit organization is supported by a GoFundMePage, and tax-deductible donations can be made through the Lightning and Love website.

The latest research funded by the foundation involved genetically engineering a zebrafish model to see if it showed symptoms of disease, specifically seizures. The zebrafish did have seizures, which Mariah said was a major breakthrough toward the ultimate goal of finding a gene replacement cure for her daughters.

But the journey for Mark and Mariah has proven to be more than just research and discovery.

What were realizing is the more we talk about it, and the more we do to get our story out there, the more were realizing that theres a lot of other parents that are going through tough times with their kids, too, Mark said. In an odd twist, or an ironic twist, this tough hand that weve been dealt has actually been a very positive light to a lot of other people out there. For me, that is just as important as the research.

The familys story was recently featured on the podcast, Go Shout Love.

The couples positive message is guiding them along the road they hope will lead to a better life for their family. But in the meantime, Mark and Mariah will continue to put smiles ontheir daughters faces the same way most other parents do by offering their love, support and opportunities to find happiness.

For Emma, that means being tossed into the air and caught by her daddy, and for Abby, it is time in her sensory room and being around her dad and her family.

Emma loves very big movements. Shes not mobile, and she cant walk, so when we kind of throw her around in the air or fly her around the room, she absolutely loves it, Mariah said. Abby loves her daddy. She gives big old smiles when he walks into the room.

To reach John F. Russell, call 970-871-4209, email jrussell@SteamboatPilot.com or follow him on Twitter @Framp1966.

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COVID-19 Vaccine and Therapeutics Pipeline Analysis Report 2020: The Race to Market as Clinical Trials Move Up a Gear – ResearchAndMarkets.com -…

September 30th, 2020 4:50 pm

DUBLIN--(BUSINESS WIRE)--The "COVID-19 Vaccine and Therapeutics Pipeline Analysis 2020" report has been added to ResearchAndMarkets.com's offering.

The report covers market characteristics, size and growth, segmentation, regional and country breakdowns, competitive landscape, market shares, trends and strategies for this market. It traces the market's historic and forecast market growth by geography. It places the market within the context of the wider COVID-19 vaccine & therapeutics pipeline analysis 2020 market, and compares it with other markets.

Major players in the COVID-19 vaccine and therapeutics pipeline analysis market are CanSino Biologics, Moderna, Inovio Pharmaceuticals, Regeneron, Gilead Sciences, GlaxoSmithKline, Medicago Inc., Sanofi, University of Oxford, and Altimmune.

The COVID-19 vaccine and therapeutics pipeline analysis market covered in this report is segmented by product type into small molecules, biologics, blood & plasma derivatives, monoclonal antibodies, vaccines, others. It is also segmented by the phase of development into preclinical therapeutics & vaccines, clinical studies, by treatment mechanism & route of administration, and by type of sponsor into pharma/biotech company, academic research/institution, others.

The COVID-19 vaccine and therapeutics pipeline analysis market report provides an analysis of the coronavirus (COVID-19) therapeutics and vaccines under development. The report includes existing vaccines developed against MERS-CoV and SARS-CoV. The novel coronavirus-2019 (nCoV-19) has been named as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses (ICTV) due to its genetic similarity with the coronavirus responsible for the 2003 SARS outbreak. Currently, government agencies, international health authorities and institutions and biopharmaceutical companies worldwide are focusing on developing vaccines/drugs to prevent or treat the COVID-19 infection.

Ever since the coronavirus hit the world as a global pandemic, many key vaccine developers are collaborating to develop potential COVID-19 vaccine against coronavirus.

Most recently, on 21st May 2020, CanSino Biologics Inc. and Precision NanoSystems announced a co-development agreement of an mRNA lipid nanoparticle (mRNA-LNP) vaccine against COVID-19. The parties will leverage Precision NanoSystems's proprietary RNA vaccine platform, comprising of lipid nanoparticle delivery system and the NanoAssemblr manufacturing technology, to rapidly advance a COVID-19 mRNA-LNP vaccine candidate towards human clinical testing and pursuant to regulatory approvals, and commercialization in different regions. Precision NanoSystems will be responsible for the development of the mRNA-LNP vaccine and CanSinoBIO will be responsible for pre-clinical testing, human clinical trials, regulatory approval and commercialization.

Similarly, on May 19, 2020, IPharmaJet, the maker of innovative, needle-free injection technology announced that its Needle-free Injection System technology will be used to deliver a messenger RNA (mRNA) vaccine against SARS-CoV-2. The vaccine is being developed by Abnova Corporation, the world's largest antibody manufacturer, based in Taiwan.

The development of potential drugs and vaccines for COVID-19 is progressing quickly. There is a massive increase in COVID-19 drugs and vaccines pipeline owing to the urgent need to contain the spread of disease. Government agencies, global health authorities and institutes, and biopharmaceutical companies are focusing on remedies to treat the patients and control the infection spread. Increasing every day, 450+ potential therapeutic candidates are under investigation. While two-thirds of the pipeline account for therapeutic drugs, the remaining one-third accounts for vaccines.

Of the confirmed active vaccine candidates, nearly 70% are being developed by private/industry developers, with the remaining 30% of projects being led by the academic, public sector and other non-profit organizations. Most COVID-19 vaccine development activity is in North America, with around 36 (46%) developers of the confirmed active vaccine candidates. China constitutes 18% with 14 developers, while, Asia excluding China and Europe also constitute 18% each with 14 developers in each region, respectively.

The long and costly drug development process is anticipated to limit the growth of the COVID-19 vaccine & therapeutics. According to the Pharmaceutical Research and Manufacturers of America (PhRMA), the average cost of research and development of a new drug is approximately $2.6 billion. Moreover, the stringent regulations imposed by the various regulatory authorities such as European Medicines Agency and the US Food and Drug Administration (FDA) in regards with clinical trials during the COVID-19 outbreak attributing to the safety of trial participants, maintaining compliance with good clinical practice, and minimizing risks to trial integrity is a major challenge faced by the COVID-19 vaccine and therapeutics market.

The compounds and medications that are under investigation can be grouped into three broad categories - antivirals, immune-system based, and vaccines. The anti-virals including Darunavir, Favipiravir, Hydroxychloroquine and chloroquine, Lopinavir, and Remdesivir (GS-5734), immune system-related therapies including Tocilizumab, Tocilizumab, and Vitamin C, and other medications are currently being evaluated as therapies. Three key drugs are currently in phase III, of which are two small molecule-based drugs, Remdesivir by Gilead Sciences Inc. and Favipiravir by Fujifilm Toyama Chemical Co Ltd, and Sarilumab, a monoclonal antibody by Regeneron Pharmaceutical. With regards to the prophylactic vaccine pipeline, more than 90% are in early-stage development (discovery and preclinical), and only three in Phase II. These three COVID-19 vaccines are being developed by Sinovac Biotech Ltd, the University of Oxford, and the third vaccine, named CIGB-2020, is being developed by the Center for Genetic Engineering and Biotechnology.

According to the European Centre for Disease Prevention and Control, worldwide, there are over 10.8 million cases of COVID-19. Globally, R&D spending has increased to find a potential drug or vaccine to combat this pandemic. Currently, there is no approved targeted therapy for patients with COVID-19. However, an array of drugs approved for other indications as well as several new investigational drugs are being studied in several hundred clinical trials. The increased R&D spending has contributed to the invention/discovery of more than 400 unique drugs to treat COVID-19 among which 298 are therapeutic drugs and 140 prophylactic vaccines that are spread across all stages of development (Discovery, Preclinical, Phase I, Phase II, and Phase III). As of June 2020, over 2,341 clinical trials are investigating potential therapies for COVID-19, of which nearly 800 are interventional trials.

Other Collaborations:

Key Topics Covered:

1. Executive Summary

2. Disease Overview

2.1. Novel Coronavirus Etiology and Pathogenesis

2.2. Novel Human Coronavirus (ClOVID-19) Clinical Features-Signs and Symptoms

3. Disease Epidemiology and Epidemic Statistics for Major countries

4. Global Pipeline Analysis of COVID-19 Therapeutics and Vaccines

4.1 Global Pipeline Analysis, By Product Type

4.1.1 Small Molecules

4.1.2 Biologics

4.1.2.1 Blood & Plasma Derivatives

4.1.2.2 Monoclonal Antibodies

4.1.2.3 Vaccines

4.1.2.4 Others

4.2 Global Pipeline Analysis, By Phase of development

4.2.1 Preclinical Therapeutics & Vaccines

4.2.2 Clinical Studies

4.2.2.1 Clinical Phase I, II, III

4.3 Global Pipeline Analysis, By Treatment Mechanism & Route of Administration

4.3.1 Mechanism of Action

4.3.1.1 Viral Replication Inhibitors

4.3.1.2 Protease Inhibitors

4.3.1.3 Immunostimulants

4.3.1.4 Other Mechanism of Action

4.3.2 Route of Administration

4.3.2.1 Oral

4.3.2.2 Intravenous

4.3.2.3 Subcutaneous

4.3.2.4 Other Route of Administration

4.4 Global Pipeline Analysis, By Type of Sponsor

4.4.1 Pharma/Biotech Company

4.4.2 Academic Research/Institution

4.4.3 Others such as Government Organizations and CROs

5. Competitive Landscape for Late Stage Therapeutics and Vaccine

5.1 Company Overview

5.2 Product Description

5.3 Research and Development

5.3.1 Non-Clinical Studies

5.3.2 Clinical Studies

5.3.3 Highest/Late Stage Development Activities

5.4 Licensing and Collaboration Agreements

5.5 Milestones & Future Plans

6. Regulatory Framework for COVID-19 Therapeutics and Vaccines Marketing Approvals

6.1 Regulatory Framework in the USA

6.2 Regulatory Framework in EU and Other Countries

7. Recommendations & Conclusion

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/yg3jj7

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Thermofluidic heat exchangers for actuation of transcription in artificial tissues – Science Advances

September 30th, 2020 4:50 pm

INTRODUCTION

Cells transform noisy environmental signals into spatial and dynamic gene expression patterns that guide biological form and function. Information describing how these transcriptional networks are patterned is exploding because of revolutions in single-cell RNA sequencing and spatial transcriptomics. Recapitulating this spatiotemporal information transfer in three-dimensional (3D) tissue settings remains a pivotal yet elusive goal of diverse fields, such as tissue engineering (1), synthetic biology (2, 3), and developmental biology (4, 5).

To control gene expression, biologists have developed diverse technologies to rewire cells at the genetic level, such as gene knockout, inhibition, overexpression, and editing (68). To further enable spatial and dynamic control of gene expression, several of these tools have been adapted to be triggered by exogenous stimuli such as light (e.g., optogenetic transcriptional control) (9, 10). Light-based actuation of gene expression patterning has been especially useful in 2D culture or optically transparent settings. However, the inherently poor penetration of light in densely populated tissues (11), long exposure times needed to activate molecular switches, and corresponding challenges in patterning light delivery have limited widespread adoption of light-based patterning of gene expression in 3D settings (12).

We hypothesized that we could overcome these challenges by exploiting more penetrant forms of energy to drive gene patterning. In particular, mild heating is an attractive option for 3D patterning across length scales, as heat can be targeted locally and penetrate tissues at depth. Furthermore, heat can diffuse through tissues to establish thermal gradients in predictable and controllable patterns that are dictated by established rules of heat transfer (13). Last, advances in molecular engineering have led to proliferation of thermal molecular bioswitches to regulate gene expression (14, 15), with mammalian systems activating in the mild hyperthermia range (~38 to 45C).

Heat transfer has a long industrial history, as heat is often added, removed, or moved between processes using heat exchangers, which transfer heat between fluidic networks. Recently, heat exchanger fabrication has undergone a radical shift due to developments in advanced manufacturing (e.g., 3D printing). Predating its history in industry, biological organisms have also long used heat exchanger design principles for thermoregulation. We reasoned that instead of building heat exchangers from hard materials, developing methods to build heat exchangers in materials compatible with living cells could facilitate volumetric heat patterning in artificial tissues.

We introduce a thermofluidic method for mesoscale spatiotemporal control of gene expression in artificial tissues that exploits volumetric fluid-based heat transfer, which we call heat exchangers for actuation of transcription (HEAT; Fig. 1A). HEAT leverages our open-source projection stereolithography bioprinting technology (16) to fabricate topologically complex fluidic channels of user-defined geometries in hydrogels (Fig. 1B, top and middle). 3D printed hydrogels are laden with genetically engineered heat-inducible cells during the printing process (Fig. 1A). Encased channel networks are perfused with precisely heated fluid from a power-supplied heating element. During perfusion, tissue temperature is monitored in real-time using an infrared camera (Fig. 1A). We find that thermofluidic perfusion facilitates heat transfer from the channels into the bulk hydrogel and enables architectural heat patterning in hydrogels (Fig. 1B, bottom).

(A) Schematic of thermofluidic workflow. A biocompatible fluid flows around a power supplied heating element to preheat the fluid before entry in perfusable channel networks within hydrogel tissue constructs laden with heat-sensitive cells. During perfusive heating, hydrogel temperature is continuously monitored using an infrared camera. (B) Perfusable channel networks of varying spatial geometries can be bioprinted within biocompatible 3D hydrogels. Top: 3D rendering of network architectures. Middle: Hydrogel channels infused with tonic water fluoresce when imaged under ultraviolet backlight. Bottom: Infrared thermography of heat-perfused hydrogels demonstrates that during perfusion, heat traces the path of fluid flow and dissipates into the bulk hydrogel. Scale bars, 5 mm.

Most mammalian thermally inducible gene switches require exposure to mild hyperthermia (39 to 45C) for prolonged periods of ~15 to 60 min to activate transcription (15, 17). We therefore tested whether this approach could precisely regulate tissue temperature over prolonged periods of time by maintaining steady-state thermal profiles in perfused hydrogels. To do this, we first printed hydrogels that contained a single channel (Fig. 2A). We then perfused precisely heated fluid through this channel while tracking hydrogel temperature in real-time using infrared thermography (Fig. 2B). Upon initiating perfusion, we observed that hydrogel temperature underwent an initial ramp-up phase (~5 min) followed by a steady-state plateau in which temperature deviated by <0.4C/min at three separate regions measured across the hydrogel (Fig. 2B, right).

(A) Photograph of a single-channel bioprinted hydrogel used for initial thermal characterization. Scale bar, 5 mm. (B) Representative infrared images from controlled perfusion of heated fluid through the channel over time (left). Scale bars, 5 mm. (C) Representative finite-element modeling images depicting steady-state predictions on the surface of perfused hydrogels at varying flow rates and constant heater power (left; full dataset in fig. S1B). Computational modeling predicts that flow rate can achieve maximal hydrogel temperatures in the mild hyperthermia temperature range (right, gray shading denotes mild hyperthermia range). (D) Hydrogels were experimentally perfused at flow rates of 0.5 and 1.0 ml min1 and imaged using infrared thermography. Scale bars, 5 mm. (E) Hydrogel temperature plotted orthogonal (x) to the flow direction at inlet and outlet positions show agreement between thermal gradients in computational and experimental measurements (computational, dashed lines; experimental, solid lines). (F) Hydrogel temperature plotted parallel (y) to flow direction demonstrates a larger temperature drop from inlet to outlet (y) during flow at 0.5 ml min1 (T0.5) compared to flow at 1.0 ml min1 (T1.0) in computational and experimental models (computational, dashed lines; experimental, solid lines; n = 5, data are mean temperature standard error, **P < 0.01 by Students t test). Photo credit: Daniel Corbett, University of Washington.

During perfusion, heat is transferred from fluidic channels to the bulk through convection and conduction, resulting in thermal gradients throughout the bulk volume (18). The perfusate input temperature is known to govern the rate and magnitude of heat transfer, while fluid flow rate influences the thermal profile (18). To determine the relative effects of perfusate temperature and flow rate on hydrogel heating at biologically relevant temperatures, we sought to develop a finite element model of heated hydrogel perfusion for mild hyperthermia that incorporated thermal and flow parameters from our heating system. To derive these parameters, we first incrementally increased flow rate over a range of heating element powers and measured fluid temperature at the point of heater outflow (i.e., hydrogel inlet; fig. S1). We then implemented perfusate temperature values observed from each flow rate at 13.5-W heater power into a computational model of single-channel hydrogel heating (Fig. 2C and fig. S1B). Computational simulations predicted that hydrogel temperatures in the range for mild hyperthermia were achievable using flow rates from 0.4 to 1.6 ml min1, but not for slower or faster flow rates (Fig. 2C and fig. S1B). Within this window, we observed that flow rates of 0.5 and 1.0 ml min1 produced subtle differences in the shape of thermal profiles, despite roughly equivalent input temperatures (Fig. 2C and fig. S1B). Thus, these flow rates provided a set of conditions to further examine the effects of flow rate on heat transfer.

We therefore performed experimental validation studies of perfused single-channel hydrogels at 0.5 or 1.0 ml min1 and analyzed the steady-state thermal profiles from infrared images (Fig. 2D). Experimental temperature measurements (solid lines) and computational simulation predictions (dashed lines) showed agreement when measured both orthogonal (Fig. 2E) and parallel (Fig. 2F) to channel flow. Both physical measurements and simulations demonstrated thermal gradients in the hydrogel. Temperature along the channel was better maintained under flow at 1.0 ml min1 compared to flow at 0.5 ml min1 (**P < 0.01; Fig. 2, E and F), and flow at 0.5 ml min1 promoted more heat transfer at the channel inlet (fig. S2A). Addition of cells to single-channel hydrogels did not affect temperature profile after thermofluidic perfusion (fig. S2B) nor did differences in hydrogel weight percent in ranges commonly used for 3D printing of cellularized hydrogels [i.e., 10 to 20 weight % (wt %); fig. S2C] (16). Stiffer hydrogel formulations (i.e., 25 wt %) did exhibit different temperatures at the hydrogel edge, although these formulations are less commonly used for bioprinting due to their limited support of cell viability (16).

These findings led us to further computationally explore the potential spatial design space for a single-channel system. To do this, we assessed how varying channel length and ambient temperature affect the thermal profile in our model. Predictions showed that single channels up to 30 mm long achieved hyperthermic temperatures (40 to 45C) along their entire length, with outlet temperatures falling out of the hyperthermic range at greater lengths (fig. S3A). Spatial heat distribution was only marginally affected within the ambient temperature range used in our studies here (20 to 22C; fig. S3B), but more substantive increases in ambient temperature (e.g., to 30, 37C) produced wider spatial gradients in hyperthermic range (fig. S3B). Together, these studies showed that the rules of heat transfer could be leveraged to predict thermal spatial profiles in perfused hydrogels and that these profiles could be finely tuned by varying parameters such as flow rate, channel length, and input and ambient temperature.

We next aimed to genetically engineer heat-inducible cells that activate gene expression upon exposure to mild hyperthermia. To do this, we implemented a temperature-responsive gene switch-based on the human heat shock protein 6A (HSPA6) promoter, which exhibits a low level of basal activity and a high degree of up-regulation in response to mild heating (19). This promoter activates heat-regulated transcription through consensus pentanucleotide sequences (5-NGAAN-3) called heat shock elements, which are binding sites for heat shock transcription factors (19). We transduced human embryonic kidney (HEK) 293T cells with a lentiviral construct in which a 476base pair (bp) region of the HSPA6 promoter containing eight canonical heat shock elements was placed upstream of a firefly luciferase (fLuc) reporter gene (Fig. 3A). Initial characterization of temperature-sensitive promoter activity in engineered cells in 2D tissue culture demonstrated a temperature-dose dependent up-regulation of luciferase activity in the range of mild hyperthermia (fig. S4A). Statistically significant up-regulation was observed in heated cells compared to nonheated controls after hyperthermia for 30 min at 45C or 60 min from 43 to 45C, while peak bioluminescence occurred after 60 min at 44C (292 26-fold increase in bioluminescence relative to 37C controls). Bioluminescent signal was first detected 8 hours after heat shock, peaked at 16 hours (110 30-fold increase), and fell back to baseline by 2 days (fig. S4B). Administration of a second heat shock stimulus 3 days later reinduced bioluminescent signal (fig. S4C). Thus, gene activation with this promoter system is transient but can be reactivated with pulsing.

(A) HEK293T cells were engineered to express fLuc under the HSPA6 promoter. (B) Schematic of thermofluidic activation of encapsulated cells. (C) Single-channel tissue used for 3D heat activation (left). Scale bar, 3 mm. Transmittance image of cellularized hydrogel after printing (middle). Scale bar, 500 m. HEK293T cells in bioprinted tissues stained with calcein-AM (live, green) and ethidium homodimer (dead, red; right). Scale bars, 200 m. (D) Representative infrared images of thermofluidic perfusion in single-channel hydrogels. Scale bars, 2 mm. (E) Hydrogel temperatures are tuned by changing heater power at constant flow rate (n = 3, mean temperature standard error). (F) Representative bioluminescence images of hydrogels (top; scale bars, 2 mm) and intensity traces at three positions (A to C) across the width (x) of the hydrogel after 30 min of perfused heating. (G) Fold change in bioluminescence after 30 min of heating relative to 25C controls. (H) Representative bioluminescence images of hydrogels (top; scale bars, 2 mm) and intensity traces after 60 min of perfused heating (bottom; scale bars, 2 mm). (I) Fold change in bioluminescence after 60 min of heating demonstrates a temperature-dependent dosage response in gene expression [(G and I); n = 3, mean fold luminescence standard error; *P < 0.05 and **P < 0.01 by one-way ANOVA followed by Dunnetts multiple comparison test]. (J) Temperature-expression response curve (black) shows mean bioluminescent radiance across temperature; shaded regions (gray) indicate SD. n = 3. Photo credit: Daniel Corbett, University of Washington.

We observed that our highest heat exposure (45C for 60 min) led to a tradeoff between bioluminescence and cell integrity, as indicated by reduced cell metabolic activity and substrate detachment (fig. S5A). These findings suggested that fine control of heat would be needed for thermofluidics to be useful in cellularized applications. We therefore rigorously characterized the effect of heating on HEK293T cells embedded in the hydrogel formulation used for our thermofluidic studies. Similar to 2D studies, cell viability fell significantly only after exposure to our highest temperature, 45C (fig. S5B). Together, these studies demonstrate engineering of human cells with a heat-sensitive gene switch and identification of a tight window of thermal exposure parameters that both differentially up-regulate gene bioluminescence and maintain cell integrity.

We sought to determine whether thermofluidic heating could be used to induce gene expression in heat-inducible cells encased within 3D artificial tissues (Fig. 3B). To do this, we encapsulated heat-inducible cells in the bulk of bioprinted constructs that contained a single perfusable channel (Fig. 3, B and C). Since tissue constructs were printed from biocompatible materials without ultraviolet light cross-linking, most cells remained viable upon encapsulation, similar to our previous studies (16) (Fig. 3C). To determine whether our heat-inducible cells could be activated using thermofluidics, we perfused channels at 0.5 ml min1 using thermal exposure parameters identified in 2D culture (Fig. 3, D and E). Similar to 2D, we observed that thermal dose-dependent luciferase up-regulation (Fig. 3, F to J) was statistically significant after 30 min of heating to a target hydrogel temperature of 44C or after 60 min of heating to temperatures of 43 and 44C by whole-gel bioluminescent output (71 22-fold and 169 44-fold increase relative to controls, respectively; Fig. 3, H and I). To more finely characterize how bioluminescent intensity correlates with temperature, infrared and bioluminescence images were overlaid to map individual pixels and generate temperature-bioluminescence response curves. The shape of temperature-response curves appeared similar in shape across various target temperatures (Fig. 3J, all data overlaid; fig. S6, individual response curves). Similar to whole-gel analyses, greater target temperatures generated the most robust activation (Fig. 3J and fig. S6). In initial studies, we noted that leakage at the hydrogel inlet or outlet could activate cells. Subsequent improvements to fluidic connectivity with a custom-printed perfusion apparatus led to higher precision thermal patterning (fig. S7; see link to open source perfusion apparatus design in Methods). Last, multiperspective imaging and bioluminescence quantification of single-channel perfused hydrogels from both top-down and cross-sectional perspectives demonstrated that reporter gene activation had a 3D radial gradient topology around each channel (fig. S8). Together, these results illustrate that thermofluidics can be used to activate varying levels of gene expression in 3D artificial tissues.

Spatial patterns of gene expression within native tissues vary widely in magnitude, scale, and spatial complexity. While we achieved variation in magnitude in our signal-channel studies, the expression profile geometry across the hydrogel remained similar at various perfusion temperatures. This raised the question of how to design heat delivery schemes that enable more spatially complex expression patterns across the hydrogel. Our thermal characterization (Fig. 2) revealed flow rate as one parameter that we could use, but changing flow rate alone imparted only subtle differences to the spatial thermal profile (Fig. 2, D to F). To identify a more perturbative and user-defined means of affecting heat distribution across the hydrogel, we turned to industrial heat transfer applications, in which heat exchangers are optimized to transfer heat between fluids by controlling parameters such as channel placement and flow pattern.

We mimicked a double pipe heat exchanger design within cellularized hydrogels by printing two channels at varying distances from one another (Fig. 4A, narrow versus wide). We then perfused hydrogels under different conditions for flow direction (concurrent versus countercurrent) and fluid temperature [hot (44C) versus cold (25C)]. Similar to our single-channel characterization, double-channel tissues showed close matching between thermal and bioluminescence profiles (Fig. 4A). Concurrent flow in narrow spaced channels created elongated spatial plateaus of heat and bioluminescence between the channels. Conversely, widely spaced hot channels generated mirror-imaged thermal and bioluminescent profiles, with distinct spatial separation between channels. Countercurrent flow patterns generated parallelogrammic thermal and bioluminescent profiles in both channel spacings. Substituting a hot channel for a cold channel attenuated bioluminescence in a manner that depended on channel spacing (Fig. 4A). Computational models of a similar bifurcating channel geometry further demonstrated how simple changes to parameters such as channel spacing can alter spatial thermal profile (fig. S9).

(A) Heat exchanger inspired designs for various flow directions, fluid temperatures, and channel architectures (schematics; left and center). Representative thermal (middle) and bioluminescent (right) images demonstrate spatial tunability of thermal and gene expression patterning. Scale bars, 5 mm. (B) Photographic image of four-armed clock-inspired hydrogel used for dynamic activation (top; channel filled with red dye). Each inlet is assigned to a local region (A to D). Schematic shows the spatial and dynamic heating pattern for the 4-day study (bottom). (C) Representative infrared (top) and bioluminescence expression (bottom) images for dynamic hydrogel activation at each day during the time course. (D) Quantification of local bioluminescent signals from regions of interest corresponding to each day of heating. Across all 4 days, regions corresponding to perfused arms had higher bioluminescent signals than nonperfused arms (n = 5, data are mean luminescence standard error; *P < 0.05 and **P < 0.01 by one-way ANOVA followed by Tukeys post hoc test).

As biological gene expression patterns are transient and fluctuating, we next tested whether thermofluidics could dynamically localize regions of gene expression over time. To do this, we printed clock-inspired constructs, in which four separate inlets converged on a circular channel (Fig. 4B, top). We then perfused heated fluid through each inlet over four consecutive days (Fig. 4B, bottom) and imaged tissues for bioluminescence. Bioluminescent images demonstrated statistically significant luciferase up-regulation for regions surrounding heated inlets compared to nonheated inlet regions on all 4 days (Fig. 4, C and D.) Together, our results illustrate that by exploiting heat transfer design principles, thermofluidics enables user-defined spatial and dynamic patterning of mesoscale gene expression patterns in 3D artificial tissues.

To test whether gene patterning could be maintained after engraftment of artificial tissues in vivo, we stimulated tissues with HEAT and implanted these tissues into athymic mice. All tissues contained HEK293T cells expressing fLuc under the control of the heat-inducible HSPA6 promoter. All tissue constructs contained a single channel and were stimulated in one of three ways: (i) thermofluidic perfusion at 44C for 60 min, (ii) bulk heating in a cell culture incubator at 44C for 60 min, or (iii) bulk exposure in a cell culture incubator to 37C. Tissues were implanted into mice immediately after heating, and bioluminescence imaging was performed 24 hours later. We found that thermofluidic spatial control of gene expression was maintained after in vivo tissue engraftment (Fig. 5A and movie S1).

(A) Artificial tissues with embedded heat-inducible fLuc HEK293T cells received 44C thermofluidic heating (channel heat, n = 5), 44C global heating (bulk heat, n = 3), or remained at 37C (no heat, n = 3) for 1 hour before immediate implantation into athymic mice. (B) Bioluminescence from implanted hydrogels (dashed lines) showed region specific signal only in channel heated hydrogels. (C) Average line profiles (top) across the width (x) of the hydrogel for inlet, middle, and outlet positions show that only channel heated gels induced a spatially coordinated response that was statistically significant (bottom) between the center (position B) and edges of the hydrogel (position A and C; channel heat, n = 5; bulk heat, n = 3; no heat, n = 3; data are mean luminescence standard error; **P < 0.01, by one-way ANOVA.

We next sought to demonstrate the modularity of our system for spatially regulating expression of the Wnt/-catenin signaling pathway, which directs diverse aspects of embryonic development, tissue homeostasis, regeneration, and disease (20). We engineered heat-inducible constructs to drive expression of three genes in the Wnt/-catenin signaling pathway: (i) R-spondin-1 (RSPO1), a potent positive regulator of Wnt/-catenin signaling (21); (ii) -catenin, a critical transcriptional coregulator that translates to the nucleus upon canonical Wnt signaling (22); and (iii) Wnt-2, a ligand that binds to membrane-bound receptors to activate the Wnt/-catenin signaling pathway. The Wnt-2 gene was also tagged with V5 (23). We engineered lentiviral constructs in which RSPO1, -catenin, or Wnt2-V5 is driven by the heat-inducible HSPA6 promoter, and mCherry is driven by a constitutive promoter [spleen focus-forming virus (SFFV); Fig. 6A]. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis of each engineered cell line for mCherry expression relative to GAPDH expression suggested lentiviral integration (fig. S10A). We then printed artificial tissues containing heat-inducible -catenin, RSPO1, or Wnt2 HEK293T cells and a single fluidic channel (Fig. 6B). Constructs were heated fluidically and then sliced into longitudinal zones (Fig. 6, A and B) to analyze expression of the Wnt family gene expression by RT-qPCR. Representative artificial tissues contained mCherry+ cells across the tissue (Fig. 6C). Immunostaining for the V5 tag fused to Wnt2 appeared higher near the heated channel compared to the gel periphery (Fig. 6C). RSPO1, -catenin, or Wnt2 expression was highest in the zone surrounding the heated channel (Fig. 6D). These results show that HEAT can be leveraged to activate expression of various family members of the Wnt/-catenin signaling pathway.

(A) Schematics of lentiviral constructs (left) and thermofluidic HEK293T tissue experiments (right). (B) Transmittance image of cellularized construct after printing (left; zones indicated by dashed lines). Infrared image of construct during heating (right). Scale bars, 1 mm. (C) mCherry+ HEK293T cells in printed tissues (left). Scale bars, 1 mm. Images of thermofluidically heated Wnt2 constructs after immunostaining for V5 tag (coexpressed with Wnt2; right; images taken near the tissues channel and periphery as indicated by insets). Scale bars, 200 m. (D) Wnt family genes were up-regulated in zone 3 of thermofluidically perfused gels compared to controls (n = 4, mean fold change standard error; *P < 0.05 and **P < 0.01 by two-way ANOVA followed by Tukeys multiple comparison test). (E) Differentiated HepaRG cells were engineered with a heat-inducible RSPO1 construct (schematic, top) and printed in single-channel hydrogels (photograph, left). Scale bars, 1 mm. After heating (infrared), HepaRGs remained viable in printed constructs (calcein). Scale bar, 200 m. (F) Thermofluidically heated RSPO-1 HepaRG hydrogels were dissected into zones 1 to 3 based on distance from the heat channel for RT-qPCR analysis at 1, 24, and 48 hours after heating. Expression fold change was normalized to no heat control samples. qPCR analysis of RSPO-1 across dissected zones (n = 5 to 10, data are mean fold change standard error; *P < 0.05 by one-way ANOVA followed by Tukeys multiple comparison test). (G) RT-qPCR analysis of pooled RNA across all zones at each time point for pericentral associated genes, glutamine synthetase, CYP1A2, CYP1A1, CYP2E1, and CYP3A4, and periportal/midzonal genes, Arg1 and E-cadherin (n = 15 to 30, data are mean fold change standard error, **P < 0.01 and *P < 0.05 by one-way ANOVA followed by Tukeys multiple comparison test). Photo credit: Daniel Corbett, University of Washington. n.s., not significant.

We reasoned that the ability to activate expression of Wnt/-catenin signaling pathway members could be useful for the emerging human organ-on-a-chip field by affecting functional cellular phenotypes in vitro. To test this, we turned to the liver, which performs hundreds of metabolic functions essential for life, including central roles in drug metabolism. To carry out these functions, hepatocytes divide the labor, with hepatocytes in different spatial locations performing different functions, a phenomenon called liver zonation. Recent studies have shown that liver zonation is regulated at the molecular level by Wnt/-catenin signaling (22), with higher Wnt activity associated with a pericentral vein phenotype and lower Wnt activity characteristic of a periportal phenotype. However, the extent to which different members of this pathway affect human zonated hepatic phenotypes remains unclear. A better understanding of this process would accelerate development of zonated human liver models for hepatotoxicity and drug metabolism studies.

We hypothesized that thermofluidic activation of RSPO1 in human hepatic cells would be sufficient to activate zonated hepatic gene expression profiles, as ectopic expression of RSPO1 in mouse liver has recently been shown to induce a pericentral zonation phenotype in vivo (24). To test this hypothesis, we transduced human HepaRG cells, an immortalized human hepatic cell line that retains characteristics of primary human hepatocytes, with our lentiviral construct in which HSPA6 drives RSPO1, and SFFV drives mCherry (Fig. 6E). Transduced human hepatic cells were then printed in artificial tissues with a single fluidic channel, to mimic central lobular placement of the central vein (Fig. 6E). Constructs were heated fluidically and then sliced into zones (Fig. 6A), and gene expression was measured by RT-qPCR (Fig. 6F). Fold up-regulation values were normalized to identically fabricated control artificial tissues maintained at 37C. We found that RSPO1 expression increased in a dose-dependent and spatially defined manner, with expression in zone 3 nearest the channel (central vein) 10-fold higher than in zone 1 by 1 hour after heating. RSPO1 expression was transient, falling with each day after heating, similar to our luciferase studies (Fig. 4C and fig. S5C). Thermofluidic activation of RSPO1 induced expression of key pericentral marker genes, including glutamine synthetase, an enzyme involved in nitrogen metabolism, and the cytochrome P450 (CYP) drug-metabolizing enzymes CYP1A2, CYP1A1, and CYP2E1 relative to control tissues that were not heated, although with varied timing and without spatial localization in this study (Fig. 6G and fig. S10). Expression of pericentral drug-metabolizing enzyme CYP3A4 was not induced with heating, consistent with other studies in which adding Wnt3a ligand to primary human hepatocyte cultures did not alter CYP3A4 expression (25). Periportal marker E-cadherin was not induced, but periportal/midzonal gene Arg1 increased at 48 hours, especially in the zone 2 midzonal region (fig. S10). Together, these studies contribute a fundamental understanding of how various liver zonation genes are induced by RSPO1 activation in human hepatic cells.

In this study, we demonstrate that thermal patterning via bioprinted fluidics can directly pattern gene expression in 3D artificial tissues. A key advantage of the HEAT method is that it leverages the recent explosion in accessible additive manufacturing tools (16, 26, 27) by using open-source bioprinting methods that are readily available to the broader community. Furthermore, the entire patterned network is stimulated nearly simultaneously (as opposed to sequentially by time-intensive rastering), and this parallel stimulation can be sustained for exposure times required to trigger gene expression. Together, the sheer rapidity and highly parallel nature of this process enable spatial and dynamic genetic patterning at length scales and depths not previously possible in 3D artificial tissues.

Most previous methods to elicit cellular signaling in artificial tissues have focused on tethering extracellular cues to hydrogels (28, 29). Innovations in stimuli-responsive or smart biomaterials enabled activation of these chemistries by exogenous physical stimuli, such as light, to control the spatial position and timing of extracellular cues (30, 31). Although useful, these material-focused methods are unlikely to provide complete control even in fully defined starting environments because cells rapidly remodel their microenvironments (32). Moreover, these technologies offer an imprecise means to control downstream transcription because many, often unknown, intermediary steps modify intracellular signal transduction before gene activation. Our thermofluidic approach provides a complementary new technology to these methods that target extracellular signals by facilitating spatiotemporal control at the intracellular genetic level.

While our studies here reveal the potential power of HEAT for gene patterning, the first-generation system presented here does have limitations in its ability to fully control heat transfer both spatially and temporally. In our studies here, we found that channels up to 30 mm long (but no longer) could achieve hyperthermic temperature ranges along the entire channel length. Furthermore, the effect of heat-mediated stimulation on gene expression was transient. These limits could be overcome through a variety of design modifications. For example, the hydrogel or perfusates thermal conductivity could be increased by materials engineering to extend patterning area or length, such as by cross-linking metal nanoparticles into the polymer backbone as has been done before for other applications (33). To achieve different activation temperatures or dynamics, further genetic engineering of the heat shock promoter or other heat-activatable gene switches could be used (14). Thus, we envision that our initial system here will establish an important foundation that leads to a new family of studies that will ultimately describe a far greater design space for thermofluidic patterning.

To fully realize the vision of precision-controlled 3D artificial tissues, a diverse toolkit of orthogonal physical delivery and molecular remote control agents will likely be needed (34, 35). Thermofluidics could be coupled with other tissue engineering strategies that program extracellular (3, 2931) or intracellular (10, 14) signal presentation, cell patterning (36), or tissue curvature (37). Thermofluidics could also be used orthogonally with other remote control agents, such as those leveraging small-molecule (12), ultrasound (38), radio wave (39), magnetic (40), or light-based activation (41). Coupled with rapid advances in gene editing (10), synthetic morphogenesis (2, 3), and stem cell technology (4, 5), thermofluidics could be useful for spatially and temporally activating genes across tissues to drive cell proliferation, fate, or assembly decisions. While we demonstrate utility for activating Wnt/-catenin signaling pathway genes here, this approach could be rapidly adapted to activate any gene of interest. In our studies, we demonstrate one application of this approach by driving human hepatic cells toward a more pericentral liver phenotype in 3D artificial tissues. In doing so, we gain fundamental insights into how activation of Wnt agonist RSPO1 regulates expression of various metabolic zonation genes. These findings have important implications for developing both organ-on-chip systems for pharmacology and hepatotoxicity, as well as artificial tissues for human therapy. By blurring the interface between the advanced fabrication and biological realms, thermofluidics creates a new avenue for bioactive tissues with applications in both basic and translational biomedicine.

Poly(ethylene glycol) diacrylate (PEGDA; 6000 Da) and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) were prepared as previously described (16, 42). Gelatin methacrylate (GelMA) was synthesized as previously described, with slight modifications (43). Methacrylic anhydride was added dropwise to gelatin dissolved in carbonate-bicarbonate buffer at 50C for 3 hours, followed by precipitation in ethanol. The precipitate was allowed to dry, dissolved in phosphate-buffered saline (PBS), frozen at 80C, and then lyophilized for up to 1 week. GelMA was stored at 20C until use. Tartrazine (Sigma-Aldrich T0388, St. Louis, MO, USA) was added to prepolymer solutions as a photoabsorber to increase print resolution as previously described (16). Prepolymer mixtures for all cellular studies contained 7.5 wt % 6 K PEGDA, 7.5 wt % GelMa with 17 mM LAP, and 1.591 mM tartrazine. For characterization of heat transfer with respect to gel density, the overall polymer weight percent was varied while holding the ratio of 6 K PEGDA to GelMA constant at 50:50 (for example, 20 wt % = 10 wt % 6 K PEGA + 10 wt % GelMa).

Hydrogels with perfusable channel networks were designed in an open-source 3D computer graphics software Blender 2.7 (Blender Foundation, Amsterdam, Netherlands) or in SolidWorks (Dassault Systemes SolidWorks Corp., Waltham, MA).

Our stereolithography apparatus for tissue engineering bioprinting system was used in this study (16). Briefly, the system contains three major components: (i) a Z-axis with stepper motor linear drive, (ii) an open-source RepRap Arduino Mega Board (UltiMachine, South Pittsburg, TN) microcontroller for Z-axis control of the build platform, and (iii) a projection system consisting of a DLP4500 Optical Engine with a 405-nm light-emitting diode output (Wintech, Carlsbad, CA) connected to a laptop for photomask projection and motor control. The projector is placed in front of the Z-axis, and a mirror is positioned at 45 to the projection light path to reflect projected images onto the build platform. A sequence of photomasks based on a 3D model is prepared using Creation Workshop software (www.envisionlabs.net/), which also controls the Z-axis movement of the build platform. Printing is achieved by curing sequential model layers of the photosensitive prepolymer. All printing was conducted in a sterile tissue culture hood. For visualization of channel networks, we perfused open channels with ultraviolet fluorescent tonic water or India ink dyes (P. Martins, Oceanside, CA).

To control temperature distribution in perfused hydrogels, an in-line fluid heater was developed to prewarm perfusate solutions before infusion in hydrogel channel networks. The fluid heater consists of four components: (i) an adjustable dc Power Supply (Yescom USA Inc., City of Industry, CA), (ii) a cylindrical cartridge heater (Uxcell, Hong Kong), (iii) perfusate tubing (peroxide-cured silicone tubing, Cole Parmer, Vernon Hills, IL), and (iv) a syringe pump (Harvard Apparatus, Holliston, MA). To construct the in-line fluid heater, perfusate tubing was connected to the syringe pump for flow rate control, while the cartridge heater was connected to the power supply for heating control. Perfusate tubing was then wounded around the cylindrical cartridge heater, allowing for heat transfer from the heater into the flowing perfusate. The temperature of the fluid was then controlled by changing the flow rate or heater power. In all studies, we used PBS (Thermo Fisher Scientific, Hampton, NH) for the perfusate solution.

To establish a fluidic connection between the heating system and hydrogel channel networks, we used custom-designed 3D printed perfusion chips printed on a MakerGear M2 3D printer (MakerGear, Beachwood, OH) in consumer-grade poly(lactic acid) plastic filament. Perfusion chips were fabricated with (i) an open cavity to insert 3D bioprinted hydrogels and (ii) attachment ports for fluid-dispensing nozzles. The outflow of the fluid heater was fitted with a male luer hose barb (Cole Parmer) connected to a flexible tip, polypropylene nozzle (Nordson EFD, East Providence, RI) and inserted into 3D printed attachment ports. Hydrogels were then inserted to perfusion chips, and proper fluidic connections were ensured before beginning perfusion. Model files for 3D printed perfusion holders are provided in the open repository data of our previously published work (16).

Fluid temperature and heat distribution were measured in perfused hydrogels by infrared thermography. Images were acquired by an uncooled microbolometer-type infrared camera (FLIR A655sc, Wilsonville, OR) that detects a 7.5- to 14.0-m spectral response with a thermal sensitivity of <0.05C and analyzed for temperature values using the FLIR ResearchIR software (Wilsonville, OR).

We built finite element models of perfused hydrogels in COMSOL 4.4 software (COMSOL AB, Burlington, MA). Simulations were run under transient conditions using the Conjugate heat transfer module and 3D printed hydrogel and housing geometries to predict the temperature distribution. The model was based on (i) forced convective heat transfer from the perfusion channel to the hydrogel volume and (ii) conductive heat transfer within the hydrogel volume.

Equation for (i): Heat transfer in a fluidCTt+CuT=pT(pAt+upA)+:S+(kT)+

Where is the fluid density, T is the temperature, C is the heat capacity at constant pressure, u is the velocity field, is the thermal expansion coefficient, pA is the absolute pressure, is the viscous stress tensor, S is the strain rate tensor, k is the fluid thermal conductivity, and Q is the heat content.

Equation for (ii)CpTt=(kT)+Q

Where is the hydrogel density, T is the temperature, k is the hydrogel thermal conductivity, and Q is the heat content.

Material properties of both the hydrogel and perfusate were modeled as water. Heat flux boundary conditions were included to model heat loss to the ambient environment, heat transfer coefficients of 5 and 30 W/(m2 * K) were applied to the sides and upper boundaries of the hydrogel, respectively, with an infinite temperature condition of 22.0C applied for all boundaries. Boundary temperature and fluid inflow conditions at the channel inlet were used to simulate the effect of changing perfusate temperature and flow rate, respectively. Model geometry was manipulated for studies on channel length and channel branching. Prescribed external temperature was varied for ambient temperature studies.

HEK293T cells were maintained in Dulbeccos modified Eagles medium (DMEM; Corning, NY, USA) supplemented with 10% (v/v) fetal bovine serum (FBS; Gibco) and 1% (v/v) penicillin-streptomycin (GE Healthcare Life Sciences, WA, USA). Differentiated HepaRG cells (Fisher Scientific) were maintained at confluence in six-well plates at a density of 2 106 cells per well in Williams E media (Lonza, MD, USA) supplemented with 5 HepaRG Thaw, Plate & General Purpose Medium Supplement (Fisher), and 1% (v/v) Glutamax (Fisher).

A vector containing a 476-bp version of the human HSPA6 promoter driving expression of fLuc reporter gene (gift of R. Schez Shouval from the Weizmann Institute of Science) was packaged into lentivirus using helper plasmids pMDLg/pRRE (Addgene no. 12251), pMD2.G (Addgene no. 12259), and pRSV-Rev (Addgene no. 12253) by cotransfection into HEK293T cells. Crude viral particles were harvested after 48 hours of transfection. For viral transduction, crude lentivirus was diluted 1:20 in DMEM containing polybrene (6 g/ml; Invitrogen), added to competent HEK293T cells in six-well tissue culture plates, and incubated overnight (Corning). The next day, virus-containing media was removed and replaced with fresh DMEM containing 10% FBS. After transduction, cells were heat-activated (see below) and flow-sorted to obtain a pure cell population.

To activate transgene expression under the HSPA6 promoter, engineered HEK293T cells were exposed to varying levels of hyperthermia in 2D and 3D. For 2D heat treatment studies, cells were seeded at 8 104 cells/cm2 in tissue culture plates 1 day before heat treatment. The next day, tissue culture plates were exposed to indicated heat treatments in thermostatically controlled cell culture incubators. Temperature was verified with a secondary method by a thermocouple placed inside the incubator. Upon completion of heat treatment, cells were returned to a 37C environment and sorted or analyzed at later time points. For the luminescent transient studies in fig. S4B, cells were lysed in TE buffer [100 mM tris and 4 mM EDTA (pH 7.5)] and stored at 4C until imaging. For the pulsed activation studies in fig. S4C, cells received two heat shocks as described previously at days 0 and 3. Luminescence was quantified across days 1 to 4 and normalized to cell counts from tissue culture plates that were processed in parallel according to each experimental temperature. For 3D heat shock studies, cells were encapsulated and printed in 3D perfusable hydrogels (see below) 1 day before heating. 3D hydrogels were then heat-perfused in a room temperature environment. Hydrogel temperature was monitored continuously with the infrared camera, and small adjustments to heater power were made as necessary to maintain a stable temperature profile. During perfused heating, outlet medium was continuously discarded. Upon completion of perfused heating, hydrogels were dismounted from the perfusion chips and returned to a cell culture incubator.

Cultured HEK293T cells were detached from tissue culture plates with 0.25% trypsin solution (Corning), counted, centrifuged at 1000 rpm for 5 min, and resuspended in liquid prepolymer (7.5 wt % 6 K PEGDA, 7.5 wt % GelMA, 17 mM LAP, and 1.591 mM tartrazine). For characterization of heat transfer with respect to cell density, cells were encapsulated in prepolymer mixtures at final densities from 0 to 24 106 cells ml1 before printing. For HEK293T expression studies, cells were encapsulated at a final density of 6 106 cells ml1. For HepaRG studies, cells were encapsulated at a final density of 2.5 106 cells ml1. Printing was performed as previously described under DLP light intensities ranging from 17 to 24.5 mW cm2, with bottom layer exposure times from 30 to 35 s and remaining layer exposure times from 12 to 17.5 s. Upon print completion, fabricated hydrogels were removed from the platform with a sterile razor blade and allowed to swell in cell culture media. Hydrogels were changed to fresh media 15 min after swelling and allowed to incubate overnight. Media was replaced the following morning. We tested the viability of both HEK293T and HepaRG cells following 3D printing by incubating cell-laden hydrogels with Live/Dead viability/cytotoxicity kit reagents (Life Technologies, Carlsbad, CA) according to manufacturers instructions. Fluorescence imaging was performed on a Nikon Eclipse Ti inverted epifluorescent microscope, and images were quantified using ImageJs built-in particle analyzer tool [National Institutes of Health, Bethesda, Maryland].

To visualize the magnitude and spatial localization of heat-induced luciferase expression, bioluminescence imaging was performed on heated cells and hydrogels using the in vivo imaging system (IVIS) Spectrum imaging system (PerkinElmer, Waltham, MA). Immediately before bioluminescence imaging, cell culture media was changed to media containing d-luciferin (0.15 mg/ml; PerkinElmer), and images were taken every 2 min until a bioluminescent maximum was reached. Images were analyzed using Living Image software (PerkinElmer). Luminescent imaging was performed from a top-down view (perspective orthogonal to hydrogel channel axis) for most studies. For cross-sectional images in fig. S8, hydrogels were manually sliced, incubated in luciferin containing media, and imaged under cross-section view (perspective parallel to hydrogel channel axis).

Data for the expression versus temperature plot was obtained by aligning thermal and bioluminescent images using MATLAB. To align the images, four reference points corresponding to the corners of the hydrogel were manually selected on both thermal and bioluminescence images. Then, an orthogonal transformation was performed on each image to align the corners of the hydrogel, after which the areas outside the selection were cropped. Pixel values from each image were then plotted against each other to produce the expression versus temperature plot.

Heat-inducible cells were generated as previously described and embedded into 3D-printed artificial tissues with single channels before being placed at 37C overnight. The next day, artificial tissues received either thermofluidic heat stimulation via flow of 44C biocompatible fluid at 1.0 ml min1 for 60 min (n = 5), global heat stimulus by being placed in a 44C tissue culture incubator for 60 min (n = 3), or were maintained in a 37C tissue culture incubator (n = 3). The artificial tissues were then immediately implanted subcutaneously on the ventral side of female NCr nude mice aged 8 to 12 weeks old (Taconic). Twenty-four hours after implantation, mice were anesthetized and injected with luciferin (15 mg/ml; PerkinElmer, Waltham, MA). Bioluminescence was then recorded via the IVIS Spectrum Imaging System (PerkinElmer). For 3D images, a custom 3D imaging unit developed by A. D. Klose and N. Paragas (44) (InVivo Analytics, New York, NY) was used. Briefly, anesthetized mice were placed into body-fitting animal shuttles and secured into the custom 3D imaging unit that uses a mirror gantry for multiview bioluminescent imaging. Collected images were then compiled and overlaid onto a standard mouse skeleton for perspective.

Line profiles in the x-direction across the inlet, middle, and outlet of 2D IVIS projection images from artificial gels were generated using Living Systems software (PerkinElmer, Waltham, MA). The three line profiles (inlet, middle, and outlet) from each artificial tissue were then averaged together with the average line profiles from the other artificial gels within each respective group (experimental group, n = 5; positive control group, n = 3; negative control group, n = 3). The average line profile of each group was then plotted, and average radiance values from positions 0.75 cm from the center of the channel (denoted positions A and C) were then statistically compared to the average radiance value at the center of the channel (position B) within each group by one-way analysis of variance (ANOVA).

Lentiviral constructs in which the HSPA6 promoter drives a Wnt family gene were subcloned using Gibson assembly by the UW BioFab facility. Human -catenin pcDNA3 was a gift from E. Fearon (Addgene plasmid no. 16828; http://n2t.net/addgene:16828; RRID: Addgene_16828) (45). Active Wnt2-V5 was a gift from X. He (Addgene plasmid no. 43809; http://n2t.net/addgene:43809; RRID:Addgene_43809) (46). RSPO1 was subcloned using a complementary DNA (cDNA) clone plasmid. (Sino Biological, Beijing, China). All plasmids contained a downstream cassette in which a constitutive promoter (SFFV) drives the reporter gene mCherry (gift from G. A. Kwong, Georgia Institute of Technology). Lentivirus was generated by cotransfection of HEK293Ts with HSPA6Wnt transfer plasmids with third-generation packaging plasmids (pMDLg/pRRE, pMD2.G, pRSV-REV) in DMEM supplemented with 0.3% Xtreme Gene Mix (Sigma-Aldrich). Crude virus was harvested starting the day after initial transfection for four consecutive days. For viral transduction, HEK293Ts at 70% confluency and HepaRGs at 100% confluency were treated with crude virus containing polybrene (8 g/ml; Sigma-Aldrich) for 24 hours. Five days following viral transduction, mCherry+ HEK293Ts were sorted from the bulk population by flow cytometry at the UW Flow analysis facility. HepaRGs were not sorted by flow cytometry. mCherry expression in positive HEK293T cell populations was performed using RT-qPCR.

To quantify Wnt regulator levels in HEAT-treated gels, HEK293Ts and HepaRGs for a given construct were encapsulated and heated in 3D hydrogels as previously described. No heat control samples remained at 37C in tissue culture incubators until RNA isolation. One to 48 hours following heat treatment, hydrogels were manually sliced into corresponding zones (1 to 3) and RNA was isolated using phenol-chloroform extraction (47). cDNA was synthesized using the Superscript III First-Strand Synthesis Kit (Thermo Fisher Scientific), and qPCR was performed using iTaq Universal SYBR Green Supermix (Biorad, Hercules, CA) on the 7900HT Real Time PCR System (Applied Biosystems, Waltham, MA). Primers for Wnt and housekeeping genes were designed and synthesized by Integrated DNA Technologies (Coraville, IA). Relative gene expression was normalized against the housekeeping gene 18S RNA calculated using the Ct method. Data are presented as the mean relative expression SEM. Data for HEK293T studies were normalized to relative expression of the Wnt target in 2D culture at 37C. Data for HEK293T mCherry expression were normalized to 18 s RNA and compared to GAPDH (also normalized to 18S RNA) expression levels. Data for HepaRG studies were normalized by relative expression of the Wnt target or pericentral/periportal gene marker to no heat control samples.

HSPA6Wnt2/V5 gels were fixed in 4% paraformaldehyde 24 hours postheating. For staining, samples are blocked overnight at room temperature in 1% bovine serum albumin, 1% normal donkey serum, 0.1 M tris, and 0.3% Triton X-100 with agitation. After blocking, samples are incubated in Anti-V5 tag antibody (Abcam, ab27671) diluted 1:100 in fresh blocking buffer and 5% dimethyl sulfoxide for 24 hours at 37C and agitation. Samples are washed and then incubated in secondary antibody diluted 1:500 in fresh blocking buffer and 5% dimethyl sulfoxide overnight at 37C and agitation. After incubation, samples are washed in PBS + 0.2% Triton X-100 + 0.5% 1-thioglycerol three times at room temperature and agitation, changing fresh buffer every 2 hours. To begin clearing, samples are incubated in clearing enhanced 3D (Ce3D) (48) solution at room temperature overnight with agitation protected from light. 4,6-Diamidino-2-phenylindole is diluted 1:500 in the Ce3D solution to counter stain for nuclei. To 3D image the cleared samples, the gels are placed on glass-bottom dishes and imaged overnight on an SP8 Resonant Scanning Confocal Microscope.

Data in graphs are expressed as the SE or SEM SD, as denoted in figure legends. Statistical significance was determined using two-tailed Students t test for two-way comparisons or one-way ANOVA or two-way ANOVA followed by Dunnetts, Sidaks, or Tukeys multiple comparison test.

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The Global CRISPR Technology Market Size Is Seeing Exponential Growth Due To The Application Of CRISPR Technology In Treating COVID-19 – GlobeNewswire

September 30th, 2020 4:50 pm

LONDON, Sept. 24, 2020 (GLOBE NEWSWIRE) -- (Companies Included: Crispr Therapeutics, Thermo Fisher Scientific, Intellia Therapeutics, Horizon Discovery, and Synthego Corporation)

In another instance, in early May, the US Food and Drug Administration (FDA) granted Sherlock Biosciences an emergency use authorization (EUA) for its COVID-19 diagnostic assay, beating out other companies and academic groups trying to use the powerful gene-editing technology to figure out who is infected with the novel coronavirus. Sherlocks test is the first FDA-authorized use of CRISPR technology for anything. Sherlocks test is a molecular diagnostic, intended to identify people who have acute SARS-CoV-2 infection. It capitalizes on a CRISPR-based technology developed in the lab of Feng Zhang, a scientist at Broad Institute of MIT and Harvard and a cofounder of Sherlock.

The Business Research Companys report titled CRISPR Technology Global Market Report 2020-30: Covid 19 Growth And Change covers the CRISPR market 2020, CRISPR technology market share by company, global CRISPR technology market analysis, global CRISPR technology market size, and CRISPR technology market forecasts. The report also covers the global CRISPR technology market and its segments. The CRISPR technology market share is segmented by product type into Cas9 and gRNA, design tool, plasmid and vector, and other delivery system products. The CRISPR technology market share is segmented by end-user into biopharmaceutical companies, agricultural biotechnology companies, academic research organizations, and contract research organizations (CROs). By application, it is segmented into biomedical, agriculture, diagnostics, and others.

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The global CRISPR technology market value is expected to grow from $685.5 million in 2019 to $1,654.2 million in 2023 at a compound annual growth rate (CAGR) of 24.6%. The application of CRISPR technology as a diagnostic tool is expected to boost CRISPR technology market growth during the period. The Sherlock CRISPR SARS-CoV-2 kit is the first diagnostic kit based on CRISPR technology for infectious diseases caused due to COVID-19. In May 2020, the US FDA (Food and Drug Administration) announced emergency use authorization of Sherlock BioSciences Inc.s Sherlock CRISPR SARS-CoV-2 kit, which is a CRISPR-based SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) diagnostic test.

This test helps in specifically targeting RNA or DNA sequences of the SARS-CoV-2 virus from specimens or samples such as nasal swabs from the upper respiratory tract, and fluid in the lungs from bronchoalveolar lavage specimens. This diagnostic kit has high specificity and sensitivity, and does not provide false negative or positive results. Widening the application of CRISPR technology for the diagnosis of infectious diseases will further increase the demand for CRISPR technology products and services and drive the CRISPR market 2020.

Several advancements in CRISPR technology are trending in the market. Advancements in technology will help in reducing errors, limiting unintended effects, improving the accuracy of the tool, widening its applications, developing gene therapies, and more. Scientists, researchers and companies are increasingly developing advanced CRISPR technologies for more precise editing and to get access to difficult to reach areas of human genome. For instance, in March 2020, scientists at University of Toronto developed CHyMErA, a CRISPR-based tool for more versatile genome editing. Similarly, in March 2020, researchers at New York genome center developed a new CRISPR screening technology to target RNA, including RNA of novel viruses like COVID.

In November 2019, researchers at ETH Zurich, Switzerland, swapped CAS9 enzyme for Cas 12a, that allowed the researchers to edit genes in 25 target sites. It is also estimated that hundreds of target sites can be modified using the above method. In October 2019, a team from MIT and Harvard developed new CRISPR genome editing approach called prime editing by combining CRISPR-Cas9 and reverse transcriptase into a single protein. The prime editing has the potential to directly edit human cells with high precision and efficiency.

The CRISPR technology market share consists of sales of CRISPR technology products and services, which is a gene-editing technology that allows researchers to alter DNA sequences and modify gene function. The revenue generated by the market includes the sales of products such as design tools, plasmid & vector, Cas9 & gRNA, and libraries & delivery system products and services that include design & vector construction, screening and cell line engineering. These products and services are used in genome editing/genetic engineering, genetically modifying organisms, agricultural biotechnology and others, which include gRNA database/gene library, CRISPR plasmid, and human stem cell & cell line engineering.

CRISPR Technology Global Market Report 2020-30: Covid 19 Growth And Change is one of a series of new reports from The Business Research Company that provide market overviews, analyze and forecast market size and growth for the whole market, CRISPR technology market segments and geographies, CRISPR technology market trends, CRISPR technology market drivers, CRISPR technology marketrestraints, CRISPR technology market leading competitors revenues, profiles and market shares in over 1,000 industry reports, covering over 2,500 market segments and 60 geographies. The report also gives in-depth analysis of the impact of COVID-19 on the market. The reports draw on 150,000 datasets, extensive secondary research, and exclusive insights from interviews with industry leaders. A highly experienced and expert team of analysts and modellers provides market analysis and forecasts. The reports identify top countries and segments for opportunities and strategies based on market trends and leading competitors approaches.

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The Global CRISPR Technology Market Size Is Seeing Exponential Growth Due To The Application Of CRISPR Technology In Treating COVID-19 - GlobeNewswire

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Novavax Initiates Phase 3 Efficacy Trial of COVID-19 Vaccine in the United KingdomClinical trial to enroll up to 10000 volunteers across the UK to…

September 30th, 2020 4:50 pm

GAITHERSBURG, Md., Sept. 24, 2020 (GLOBE NEWSWIRE) -- Novavax, Inc. (Nasdaq: NVAX), a late stage biotechnology company developing next-generation vaccines for serious infectious diseases, today announced that it has initiated its first Phase 3 study to evaluate the efficacy, safety and immunogenicity of NVX-CoV2373, Novavax COVID-19 vaccine candidate. The trial is being conducted in the United Kingdom (UK), in partnership with the UK Governments Vaccines Taskforce, and is expected to enroll and immunize up to 10,000 individuals between 18-84 (inclusive) years of age, with and without relevant comorbidities, over the next four to six weeks.

With a high level of SARS-CoV-2 transmission observed and expected to continue in the UK, we are optimistic that this pivotal Phase 3 clinical trial will enroll quickly and provide a near-term view of NVX-CoV2373s efficacy, said Gregory M. Glenn, M.D., President, Research and Development at Novavax. The data from this trial is expected to support regulatory submissions for licensure in the UK, EU and other countries. We are grateful for the support of the UK Government, including from its Department of Health and Social Care and National Institute for Health Research, to advance this important research.

NVX-CoV2373 is a stable, prefusion protein made using Novavax recombinant protein nanoparticle technology that includes Novavax proprietary MatrixM adjuvant. The vaccine has a favorable product profile that will allow handling in an unfrozen, liquid formulation that can be stored at 2C to 8C, allowing for distribution using standard vaccine channels.

Novavax has continued to scale-up its manufacturing capacity, currently at up to 2 billion annualized doses, once all capacity has been brought online by mid-2021.

About the Phase 3 Study

Consistent with its long-standing commitment to transparency and in order to enhance information-sharing during the worldwide pandemic, Novavax will be publishing its UK study protocol in the coming days.

The UK Phase 3 clinical trial is a randomized, placebo-controlled, observer-blinded study to evaluate the efficacy, safety and immunogenicity of NVX-CoV2373 with Matrix-M in up to 10,000 subjects aged 18 to 84 years. Half the participants will receive two intramuscular injections of vaccine comprising 5 g of protein antigen with 50 g MatrixM adjuvant, administered 21 days apart, while half of the trial participants will receive placebo.

The trial is designed to enroll at least 25 percent of participants over the age of 65 as well as to prioritize groups that are most affected by COVID-19, including racial and ethnic minorities. Additionally, up to 400 participants will also receive a licensed seasonal influenza vaccine as part of a co-administration sub-study.

The trial has two primary endpoints. The first primary endpoint is first occurrence of PCR-confirmed symptomatic COVID-19 with onset at least 7 days after the second study vaccination in volunteers who have not been previously infected with SARS-CoV-2. The second primary endpoint is first occurrence of PCR-confirmed symptomatic moderate or severe COVID-19 with onset at least 7 days after the second study vaccination in volunteers who have not been previously infected with SARS-CoV-2. The primary efficacy analysis will be an event-driven analysis based on the number of participants with symptomatic or moderate/severe COVID-19 disease. An interim analysis will be performed when 67% of the desired number of these cases has been reached.

For further information, including media-ready images, b-roll, downloadable resources and more, click here.

About NVX-CoV2373

NVXCoV2373 is a vaccine candidate engineered from the genetic sequence of SARSCoV2, the virus that causes COVID-19 disease. NVXCoV2373 was created using Novavax recombinant nanoparticle technology to generate antigen derived from the coronavirus spike (S) protein and contains Novavax patented saponin-based Matrix-M adjuvant to enhance the immune response and stimulate high levels of neutralizing antibodies. NVX-CoV2373 contains purified protein antigens and cannot replicate, nor can it cause COVID-19. In preclinical trials, NVXCoV2373 demonstrated indication of antibodies that block binding of spike protein to receptors targeted by the virus, a critical aspect for effective vaccine protection. In its the Phase 1 portion of its Phase 1/2 clinical trial, NVXCoV2373 was generally well-tolerated and elicited robust antibody responses numerically superior to that seen in human convalescent sera. NVX-CoV2373 is also being evaluated in two ongoing Phase 2 studies, which began in August; a Phase 2b trial in South Africa, and a Phase 1/2 continuation in the U.S. and Australia. Novavaxhas secured$2 billionin funding for its global coronavirus vaccine program, including up to$388 millionin funding from theCoalition for Epidemic Preparedness Innovations(CEPI).

About Matrix-M

Novavax patented saponin-based Matrix-M adjuvant has demonstrated a potent and well-tolerated effect by stimulating the entry of antigen-presenting cells into the injection site and enhancing antigen presentation in local lymph nodes, boosting immune response.

About Novavax

Novavax, Inc.(Nasdaq:NVAX) is a late-stage biotechnology company that promotes improved health globally through the discovery, development, and commercialization of innovative vaccines to prevent serious infectious diseases.Novavaxis undergoing clinical trials for NVX-CoV2373, its vaccine candidate against SARS-CoV-2, the virus that causes COVID-19. NanoFlu, its quadrivalent influenza nanoparticle vaccine, met all primary objectives in its pivotal Phase 3 clinical trial in older adults. Both vaccine candidates incorporate Novavax proprietary saponin-based Matrix-M adjuvant in order to enhance the immune response and stimulate high levels of neutralizing antibodies.Novavaxis a leading innovator of recombinant vaccines; its proprietary recombinant technology platform combines the power and speed of genetic engineering to efficiently produce highly immunogenic nanoparticles in order to address urgent global health needs.

For more information, visit http://www.novavax.com and connect with us on Twitter and LinkedIn.

Novavax Forward-Looking Statements

Statements herein relating to the future ofNovavaxand the ongoing development of its vaccine and adjuvant products are forward-looking statements.Novavaxcautions that these forward-looking statements are subject to numerous risks and uncertainties, which could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include those identified under the heading Risk Factors in the Novavax Annual Report on Form 10-K for the year endedDecember 31, 2019, and Quarterly Report on Form 8-K for the period endedJune 30, 2020, as filed with theSecurities and Exchange Commission(SEC). We caution investors not to place considerable reliance on forward-looking statements contained in this press release. You are encouraged to read our filings with theSEC, available atsec.gov, for a discussion of these and other risks and uncertainties. The forward-looking statements in this press release speak only as of the date of this document, and we undertake no obligation to update or revise any of the statements. Our business is subject to substantial risks and uncertainties, including those referenced above. Investors, potential investors, and others should give careful consideration to these risks and uncertainties.

Contacts:

Novavax

InvestorsSilvia Taylor and Erika Trahanir@novavax.com240-268-2022

MediaBrandzone/KOGS CommunicationEdna Kaplankaplan@kogspr.com617-974-8659

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Novavax Initiates Phase 3 Efficacy Trial of COVID-19 Vaccine in the United KingdomClinical trial to enroll up to 10000 volunteers across the UK to...

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Orgenesis to acquire regenerative medicine company Koligo Therapeutics – Pharmaceutical Business Review

September 30th, 2020 4:49 pm

');},success: function(response) {$('.megamenuthird[data-menu=' + $data_megamenu + '-articles]').html(response);},error: function(xhr) { // if error occured$('.megamenuthird[data-menu=' + $data_megamenu + '-articles]').html("Error occured.please try again"); }});}}//Child Level Menu Hoverfunction get_childlevelmenu(currentid){//console.log('current id '+currentid);var $currentelement = $('#'+currentid);$('.menu-item-'+$('#'+currentid).closest('.themegamenu').attr('cid').split('-')[3]).removeClass('defaultajax-1');var $data_menu = $('#'+currentid).closest('li').data('menu');var ajaxreplaceContent = $('#'+currentid).closest('.themegamenu').data('megamenu')+'-articles';var submenu = $data_menu.split('-');var data_menu_class=submenu[0];//$('.megamenuthird').empty();$('.megamenuthird[data-menu=' + ajaxreplaceContent + ']').empty();$('li.level_2').removeClass('activeli');$currentelement.closest('li').siblings().removeClass('activeli');$currentelement.closest('li').addClass('activeli');var current_megamenu_second = $('.megamenusecond[data-menu='+$data_menu+']').length;$('.megamenuopen .megamenusecond').removeClass('megamenusecond-show');//$currentelement.closest('li').find('.megamenuopen .megamenusecond').removeClass('megamenusecond-show');$('.megamenusecond[data-menu=' + $data_menu + ']').addClass('megamenusecond-show');//if(current_megamenu_seconda').html();/********* End level3 checking menu ********/// checking 4th level menu /*** 4th level Objec code here **///getting parent data-menuvar levelfour_data_menu = $('.megamenusecond[data-menu='+$data_menu+']').find('li.level_3.activeli').data('menu');// End getting parent data-menuvar subofSubChildLevel_cat_id = $('.megamenusecond[data-menu='+levelfour_data_menu+']').find('li.level_4.activeli').data('cat');var subofSubChildLevel_data_menu = $('.megamenusecond[data-menu='+levelfour_data_menu+']').find('li.level_4.activeli').data('menu');var subofSubChildLevel_taxnomy_type= $('.megamenusecond[data-menu='+levelfour_data_menu+']').find('li.level_4.activeli').data('type');var subofSubChildLevel_title = $('.megamenusecond[data-menu='+levelfour_data_menu+']').find('li.level_4.activeli>a').html();if(subofSubChildLevel_title!=''){var ajx_title=subofSubChildLevel_title;}else{var ajx_title=subChildLevel_title;}/*** End 4th level Objec code here **/if(subofSubChildLevel_cat_id!=''){var data_obj ={'title':ajx_title,'subofSubChildLevel_cat_id':subofSubChildLevel_cat_id,'subofSubChildLevel_taxnomy_type':subofSubChildLevel_taxnomy_type,'subChildLevel_cat_id': subChildLevel_cat_id,'subChildLevel_taxnomy_type' :subChildLevel_taxnomy_type,'ChildLevel_data_type':ChildLevel_data_type,'ChildLevel_data_cat_id':ChildLevel_data_cat_id,'parent_data_cat_id':parent_data_cat_id,'parent_data_type':parent_data_type};}else{var data_obj ={'title':ajx_title,'subChildLevel_cat_id': subChildLevel_cat_id,'subChildLevel_taxnomy_type' :subChildLevel_taxnomy_type,'ChildLevel_data_type':ChildLevel_data_type,'ChildLevel_data_cat_id':ChildLevel_data_cat_id,'parent_data_cat_id':parent_data_cat_id,'parent_data_type':parent_data_type};}} if( ajaxRequestProject != null ) {ajaxRequestProject.abort();ajaxRequestProject = null;}ajaxRequestProject = $.ajax({type: 'POST',url: 'https://www.pharmaceutical-business-review.com/wp-admin/admin-ajax.php?action=mega_posts',data: data_obj, dataType: "html",beforeSend: function() {$('.megamenuthird[data-menu=' + ajaxreplaceContent+ ']').html('');},success: function(response) {$('.megamenuthird[data-menu=' + ajaxreplaceContent + ']').html(response);},error: function(xhr) { // if error occured$('.megamenuthird[data-menu=' + ajaxreplaceContent + ']').html("Error occured.please try again");}});}//Subchild Level Menu Hover//Child Level Menu Hoverfunction get_subchildlevelmenu(currentid){var $currentelement = $('#'+currentid);$('.menu-item-'+$('#'+currentid).closest('.themegamenu').attr('cid').split('-')[3]).removeClass('defaultajax-1');var $data_menu = $currentelement.closest('li').attr('data-menu'); 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$target.focus(); if ($target.is(":focus")) { // Checking if the target was focused return false; } else { $target.attr('tabindex','-1'); // Adding tabindex for elements not focusable $target.focus(); // Set focus again }; }); } } }); /******** onclick share button in catgeory page ******/ $(".share-button").click(function(){ if($(this).parent('.open-share').length == 0){ $('.share').removeClass('open-share'); $(this).parent('.share').addClass("open-share"); }else{ $('.share').removeClass('open-share'); } }); /************* Mobile menu js *******/ function openNav() { document.getElementById("mobilemenu").style.width = "100%"; document.getElementById("mobilemenu").style.left = "0px"; } function closeNav() { document.getElementById("mobilemenu").style.width = "0"; } $( ".mobilemenuicon" ).click(function() { setTimeout(function(){ $( '.mobile-menu-cta' ).addClass("mobilectashow"); }, 500); }); $( ".closebtn" ).click(function() { $( '.mobile-menu-cta' ).removeClass("mobilectashow") }); /********** End mobile menu js *******/ /********* contractors Single page close Header**/ $(".close_section").click(function(){ $('.headersf').hide(1000); $('.headersf').addClass('section_closed'); $('.header-singleproduct').addClass('margin_top_added'); $('.small_header_sf').addClass('small_header_sf_display'); }); /******* End contractors Single page close Header**/ /*** My accout drop down menu */ $('.ctanav .dropdown-menu a').on('click', function() { window.location.href = $(this).attr('href'); }); /*** cookie-popup **/ $("#cookiepopup-continue").click(function(){ $.cookie("cookie_compelo", 'https://www.pharmaceutical-business-review.com'); $('.home_timeline').hide(); }); $(window).on("load",function(){ var data = $.cookie("cookie_compelo"); if(data){ $('.home_timeline').hide(); }else{ $('.home_timeline').show(); } }); $(".home_timeline .close").click(function(){ $.cookie("cookie_compelo", 'https://www.pharmaceutical-business-review.com'); $('.home_timeline').hide(); }); $(window).on("load",function(){ var data = $.cookie("cookie_compelo"); if(data){ $('.home_timeline').hide(); }else{ $('.home_timeline').show(); } }); /*** End cookie popup **/ /**** New add js code ***/ if ($(window).width() > 960) { // Initialization $(function(){ $('[data-scroll-speed]').moveIt(); }); } /* Sticky sidebar banner EVENT PAGE */ $(function(){ $(document).scroll(function(){ var scroll = $(window).scrollTop(); if (scroll >= 655) { $('.sticky-mpu-event').addClass("banner-fixed"); } else{ $('.sticky-mpu-event').removeClass("banner-fixed"); } }); }); //advertising page jQuery.fn.moveIt = function(){ var $window = jQuery(window); var instances = []; jQuery(this).each(function(){ instances.push(new moveItItem($(this))); }); window.addEventListener('scroll', function(){ var scrollTop = $window.scrollTop(); instances.forEach(function(inst){ inst.update(scrollTop); }); }, {passive: true}); } var moveItItem = function(el){ this.el = jQuery(el); this.speed = parseInt(this.el.attr('data-scroll-speed')); }; moveItItem.prototype.update = function(scrollTop){ this.el.css('transform', 'translateY(' + -(scrollTop / this.speed) + 'px)');};// InitializationjQuery(function(){jQuery('[data-scroll-speed]').moveIt();}); /**** end new add js code **/

See the rest here:
Orgenesis to acquire regenerative medicine company Koligo Therapeutics - Pharmaceutical Business Review

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