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Archive for the ‘Genetic Engineering’ Category

Cell Culture Market : Investigation and Growth Forecast until the End of 2025 Cole Reports – Cole of Duty

Friday, May 1st, 2020

In this report, the Global Cell Culture Market is valued at USD 11,210.7 million in 2015 and growing at a CAGR of over 10% between 2017 and 2025.Cell Culture Market , published by Xpodence Research, provides extensive insight and analysis of the Cell Culture Market over the next eight years (2015-2025) and acts as a vital point of reference for operators or suppliers.Increasing R&D activities of healthcare, biological, and stem cell applications has enhanced the demand of molecular biological activities which is further projected to persist a vibrant aspect for market growth. Cell culture technology includes several complications including raw material supply and fully traceable botanical extracts. Also, growing attention on certifying regulatory compliances associated with environmental sustainability can impede the efficacy of the technology.

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Additionally, affluence from various applications such as genetic engineering, research model systems, and continuous research related to cellular functions and stem cell research is also expected to drive the cell culture process globally. Few other factors spurring the growth includes rise in life sciences research, cell based technology advancement, cumulative cell based production, and mounting demand of cell based therapies.Rising growth in the number of regulatory approvals for cell culture-based vaccines and increasing funding for cell-based research will also influenced the market positively. Furthermore, growing application of single-use technologies and rising demand for mAbs are few factor projected to spur the market growth. Though, extensive cost involvement in cell culture research, lack of awareness for diagnosis technologies, and high contamination risks may hinder the market growth. Furthermore, optimization & handling of cell-based protocol in vitro studies will defies the market growth.

The report includes Segmentation: On the basis of product, this report displays the revenue, market share and growth rate of each type, primarily split into Consumables Instrument

On the basis on the applications, this report focuses on the status and outlook for major applications, market share and growth rate for each application, including Biopharmaceuticals Drug Development Cancer Research Culture Systems Gene Therapy Toxicity Testing Tissue Culture & Engineering Vaccine Production

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Geographic Segmentation: This report split global market into North America, Europe, Asia Pacific, the Middle East and Africa and Latin America, with revenue (Million USD), market share and growth rate of Cell Culture for these regions, from 2015 to 2025 (forecast)North America: U.S., Rest of North AmericaEurope: Germany, France, UK, rest of EuropeAsia Pacific: China, Japan, India and Rest of Asia PacificMiddle East & Africa: GCC, North Africa, South Africa and Rest of MEALatin America: Brazil and Rest of Latin America

Key players: Overview of market leaders in Cell Culture market by top manufacturers/players, with Cell Culture revenue (Million USD) and market share for each manufacturer/player; the top players including Sartorius AG, Thermo Fisher Scientific, Merck KGaA, Corning Incorporation, Sigma Aldrich Co. LLC, Promocell GmbH, GE Healthcare, Eppendorf AG, Becton, Dickinson & Company and VWR International, LLC.On the basis of end-users, the market shows the revenue, global share and growth rate of each type, majorly divided into

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About Kenneth Research:

Kenneth Research provides market research reports to different individuals, industries, associations and organizations with an aim of helping them to take prominent decisions. Our research library comprises of more than 10,000 research reports provided by more than 15 market research publishers across different industries. Our collection of market research solutions covers both macro level as well as micro level categories with relevant and suitable market research titles. As a global market research reselling firm, Kenneth Research provides significant analysis on various markets with pure business intelligence and consulting services on different industries across the globe. In addition to that, our internal research team always keep a track on the international and domestic market for any economic changes impacting the products demand, growth and opportunities for new and existing players.

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Kenneth ResearchEmail: [emailprotected]Phone: +1 313 462 0609

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22nd Century Group to Announce First Quarter 2020 Financial Results on May 7, 2020 – GlobeNewswire

Friday, May 1st, 2020

Williamsville, NY, April 28, 2020 (GLOBE NEWSWIRE) -- 22nd Century Group, Inc. (NYSE American: XXII) (22nd Century or the Company), a leading plant biotechnology company focused on reduced nicotine tobacco and hemp/cannabis plant genetics research and development, will release first quarter 2020 financial results on Thursday, May 7, 2020, before the market opens. The press release will be available on 22nd Century Groups website at http://www.xxiicentury.com. In conjunction with the earnings release, the Company will host a conference call on Thursday, May 7, 2020, at 8:00 a.m. ET.

The live audio webcast will be accessible in the Events section on the Company's Investor Relations website at http://www.xxiicentury.com/investors. Participants may also listen to the live call by dialing (877) 407-6914. A replay of the call will be available until May 21, 2020 by dialing (877) 660-6853; the passcode is 13702417. An archived replay of the webcast will also be available shortly after the live event has concluded.

Investors, analysts and members of the media interested in submitting questions in advance can do so by sending an e-mail to investorrelations@xxiicentury.com.

About 22nd Century Group, Inc.22nd Century Group, Inc. (NYSE AMERICAN: XXII) is a leading plant biotechnology company focused on technologies that alter the level of nicotine in tobacco plants and the level of cannabinoids in hemp/cannabis plants through genetic engineering, gene-editing and modern plant breeding. The Companys primary mission in tobacco is to reduce the harm caused by smoking by bringing its proprietary reduced nicotine content cigarettes with 95% less nicotine than conventional cigarettes to adult smokers in the U.S. and international markets. The Companys primary mission in hemp/cannabis is to develop proprietary hemp/cannabis plants with unique cannabinoid profiles and desirable agronomic traits and to commercialize those plants through a synergistic portfolio of strategic partnerships in the hemp/cannabis industry.

Learn more atxxiicentury.com, on Twitter@_xxiicenturyand onLinkedIn.

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Merck & Co. Partnering with ISB to Study Targets for COVID-19 Therapeutics – Genetic Engineering & Biotechnology News

Wednesday, April 29th, 2020

Merck & Co. said today it will partner with the Institute for Systems Biology (ISB) to identify targets for medicines and vaccines against COVID-19 by investigating and defining the molecular mechanisms of the disease and specifically SARS-CoV-2 infection.

While the value of the collaboration was not disclosed in the announcement, Merck and ISB did say they will use a contract awarded to the pharma giant in 2016 by the Biomedical Advanced Research and Development Authority (BARDA). That contract (HHSO100201600031C) has a potential value of $78.5 million ($78,531,649), and was originally awarded August 29, 2016, to advance development of the vaccine candidate V920 against Ebola virus using a recombinant vesicular stomatitis virus vector, according to a contract summary published by GovTribe.

The contract has been extended from its scheduled end of May 31, 2020, through September 30, 2024.

In December, Merck announced FDA approval of the vaccine under the name ERVEBO (Ebola Zaire Vaccine, Live), indicated for the prevention of disease caused byZaire ebolavirusin individuals 18 years of age and older.

Merck said it had agreed to provide research funding and work with researchers at ISB to characterize targets for potential therapeutic intervention and vaccine development.

Through the collaboration with Merck, scientists from ISB, health workers from the Swedish Medical Center, and a consortium of research organizations and biomedical companies plan to analyze blood samples and nasal swabs from Swedish Medical Center patients with SARS-CoV-2 using samples from several time points that include initial presentation, acute illness and convalescence.

Merck and ISB said proteomic, metabolomic, transcriptomics and genetic techniques will be applied toward examining blood samples, with the aim of evaluating the impact of infection on different organs, and identifying potential biomarkers to predict the risk of severe disease.

In addition, samples will be analyzed to create a profile of the immune response, including quantitative changes in immune cells in patients following SARS CoV-2 infection and characterization of neutralizing antibodies in samples from convalescent patients. These insights can be used to inform vaccine design and antibody therapy, Merck and ISB reason.

The study will initially analyze samples from 200 patients with the potential to expand to 300, Merck and ISB said.

The announcement is Mercks first regarding development of a potential COVID-19 therapeutic. Last month, Merck announced donations of 500,000 personal protective masks to New York City Emergency Management and 300,000 masks to New Jerseys Office of Homeland Security and Preparedness, both toward urgent efforts to address COVID-19 emergency response.

This collaboration with Merck provides critical support for the recently launched scientific trial being co-led by ISB and Swedish Medical Center, both part of the Providence St. Joseph Health network. We launched this trial with the urgent need to improve our understanding of COVID-19, James R. Heath, PhD, president and professor at ISB, said in a statement. By applying the full power of our systems biology capabilities, we hope to gain important insights into the molecular basis for the dramatically contrasting outcomes observed for patients infected with SARS-CoV-2.

Heath and Jason D. Goldman, MD, at Swedish Medical Center, will be the studys principal investigators.

Initial funding support for the study came from the Wilke Family Foundation, M.J. Murdock Charitable Trust, Swedish Foundation, Parker Institute for Cancer Immunotherapy, and Washington State Andy Hill CARE Fund. Other research collaborators on the study include Stanford University, Adaptive Biotechnologies, Bloodworks Northwest, Isoplexis, Metabolon, Nanostring, Olink, Providence Molecular Genomics Laboratory, Scisco Genetics and 10x Genomics.

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22nd Century Group to Announce First Quarter 2020 Financial Results on May 7, 2020 – Yahoo Finance

Wednesday, April 29th, 2020

Williamsville, NY, April 28, 2020 (GLOBE NEWSWIRE) -- 22nd Century Group, Inc. (NYSE American: XXII) (22nd Century or the Company), a leading plant biotechnology company focused on reduced nicotine tobacco and hemp/cannabis plant genetics research and development, will release first quarter 2020 financial results on Thursday, May 7, 2020, before the market opens. The press release will be available on 22nd Century Groups website at http://www.xxiicentury.com. In conjunction with the earnings release, the Company will host a conference call on Thursday, May 7, 2020, at 8:00 a.m. ET.

The live audio webcast will be accessible in the Events section on the Company's Investor Relations website at http://www.xxiicentury.com/investors. Participants may also listen to the live call by dialing (877) 407-6914. A replay of the call will be available until May 21, 2020 by dialing (877) 660-6853; the passcode is 13702417. An archived replay of the webcast will also be available shortly after the live event has concluded.

Investors, analysts and members of the media interested in submitting questions in advance can do so by sending an e-mail to investorrelations@xxiicentury.com.

About 22nd Century Group, Inc.22nd Century Group, Inc. (NYSE AMERICAN: XXII) is a leading plant biotechnology company focused on technologies that alter the level of nicotine in tobacco plants and the level of cannabinoids in hemp/cannabis plants through genetic engineering, gene-editing and modern plant breeding. The Companys primary mission in tobacco is to reduce the harm caused by smoking by bringing its proprietary reduced nicotine content cigarettes with 95% less nicotine than conventional cigarettes to adult smokers in the U.S. and international markets. The Companys primary mission in hemp/cannabis is to develop proprietary hemp/cannabis plants with unique cannabinoid profiles and desirable agronomic traits and to commercialize those plants through a synergistic portfolio of strategic partnerships in the hemp/cannabis industry.

Learn more atxxiicentury.com, on Twitter@_xxiicenturyand onLinkedIn.

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Mei Kuo22nd Century Group, Inc.(716) 300-1221mkuo@xxiicentury.com

John MillsICR(646) 277-1254john.mills@icrinc.com

Deirdre ThomsonICR(646) 277-1283deirdre.thomson@icrinc.com

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22nd Century Group to Announce First Quarter 2020 Financial Results on May 7, 2020 - Yahoo Finance

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Where are GMO crops grown? GLP infographics document the global growth of agricultural biotechnology innovation – Genetic Literacy Project

Wednesday, April 29th, 2020

One of the more popular claims by critics of GMOs is that only a few countries grow genetically engineered crops, led by the United States, Canada, Brazil and Argentina. Thats just not true. Its a worldwide phenomenon, and breakthroughs continued this year with the introduction of GMO crops in Kenya and Nigeria, and the anticipated rollout of Golden Rice in the Philippines.

To set the record straight, the Genetic Literacy Project has released Where GMO Crops are Grown, a combination of two linked infographics that illustrate the explosive growth worldwide in the use of transgenic seeds over the past three decades. [click on infographic to display pdf]

Designed by GLP data visualization specialist Kayleen Schreiber, the graphics document the introduction of 22 different crops developed in 41 different countries through transgenics (GMO), gene editing or other New Breeding Techniques. As the first of the two infographics illustrate, not all the countries that have introduced genetically modified crops over the past 28 years are still growing them, and some countries that still grow them have discontinued various crops for political or economic reasons.

For example, the first GMO crop commercialized in the US was the FLAVR SAVR tomato, engineered to extend its shelf life and minimize fruit softening. It fell short of expectations and its producer, Calgene, discontinued sales. Currently, 28 nations grow nearly 200 million hectares of genetically engineered plants every year, a roughly 113-fold increase from 1.7 million hectares in 1996. Biotech crops are the fastest-adopted technology in the history of modern agriculture.

The second infographic can be accessed by clicking on the purple box on the right side of the map, which launches an animation documenting when each of the 41 countries commercialized its first biotech crop. [click on infographic to display pdf]

The two graphics can be downloaded together here, or you can download each graphic separately: Where GMO Crops are Grown or 41 Countries Planted Their First Genetically Altered Crop, 1992-2020.

An evolving story emerges from these infographics. While many nations have embraced genetic engineering and never looked back, 13 of 41 countries have stopped cultivating biotech crops altogether. Burkina Faso, for example, under huge political pressure, halted the cultivation of GMO insect-resistant Bt cotton in 2015, leaving its farmers to face increased pesticide exposure and higher production costs.

Meanwhile, other nations, like China, are close to green-lighting many different plant varieties, and import many GMO crops, but currently only allow their farmers to grow a limited number of genetically engineered crops. Because of this tangled regulatory web, just five nationsthe US, Canada, Brazil, Argentina and Indiacultivate roughly 90 percent of the worlds total biotech crop acreage.

Kayleen Schreiber, neuroscientist and science communicator, is director of the GLPs gene-editing tracker and index. Follow her on Twitter @KSPHD.

Cameron J. English is the GLPs senior agricultural genetics and special projects editor. Follow him on Twitter @camjenglish

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Precision BioSciences Announces Presentations at the American Society of Gene & Cell Therapy 23rd Annual Meeting – BioSpace

Wednesday, April 29th, 2020

DURHAM, N.C., April 28, 2020 (GLOBE NEWSWIRE) -- Precision BioSciencesInc. (Nasdaq: DTIL), a life sciences company dedicated to improving life through the application of its pioneering, proprietary ARCUS gene editing platform, today announced that the Company and its collaborators will present at the upcoming American Society of Genetic & Cell Therapy (ASGCT) Annual Meeting held virtually May 12-15, 2020.

The abstracts being presented by Precision and our collaborators this year at ASGCT underscore the differentiated capabilities of our proprietary ARCUS genome editing platform and the breadth of our emerging pipeline applying this technology in vivo, commented Derek Jantz, Chief Scientific Officer and co-founder of Precision BioSciences. These presentations demonstrate the specificity and versatility of ARCUS-driven genome editing in a variety of large animal models and provide further preclinical evidence of potentially meaningful and durable therapeutic impact on a range of genetic and infectious diseases. As we continue to validate ARCUS potential in vivo, we are focused on advancing our gene correction pipeline. We look forward to selecting a clinical candidate for our wholly owned PH1 program, expected in 2020, and, in partnership with Gilead, developing a potential cure for chronic hepatitis B infection, for which submission of an IND is currently targeted for 2021.

Precision BioSciences Presentations:

Title:Engineering a Self-Inactivating Adeno-Associated Virus (AAV) Vector for ARCUS Nuclease DeliveryPoster Session: Gene Targeting and Gene Correction, Abstract: 654Presenting Author: Hui Li, Ph.D., Precision BioSciences

Title:A Gene Editing Approach to Eliminate Hepatitis B Virus Using ARCUS MeganucleasesPoster Session: Gene Targeting and Gene Correction, Abstract 1057Presenting Author: Cassie Gorsuch, Ph.D., Precision BioSciences

Partnered Presentations:

Title: Therapeutic Efficacy of ARCUS Meganuclease Gene Editing - Arrest of Rod Degeneration and Restoration of Rod Function in a Transgenic Pig Model of Autosomal Dominant Retinitis PigmentosaOral Presentation: Gene Therapy for the Special Senses, Abstract 2Date/Time: Tuesday, May 12, 2020, 10:30 10:45 a.m. ESTPresenting Author: Maureen Ann McCall, Ph.D., Professor, Department of Ophthalmology and Visual Sciences, University of Louisville

Title: Evaluation of the Long-term Effects of AAV-Meganuclease Genome Editing of PCSK9 in Macaque LiverOral Presentation: Evaluating Genome Editing Activity and Precision, Abstract 518Date/Time: Wednesday, May 13, 2020, 4:00 4:15 p.m. ESTPresenting Author: Lili Wang, Ph.D., Research Director, Discovery Research and Gene Editing, Research Associate Professor, Department of Medicine, Perelman School of Medicine, University of Pennsylvania

All abstracts for the ASGCT 2020 Meeting are available online at ASGCT Annual Meeting Abstracts.

About Precision BioSciences, Inc.Precision BioSciences is dedicated to improving life (DTIL) through its proprietary genome editing platform, ARCUS. Precision leverages ARCUS in the development of its product candidates, which are designed to treat human diseases and create healthy and sustainable food and agriculture solutions. Precision is actively developing product candidates in three innovative areas: allogeneic CAR T immunotherapy, in vivo gene correction, and food. For more information regarding Precision, please visitwww.precisionbiosciences.com.

Forward-LookingStatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including the timing of trials and results from clinical and non-clinical studies of our in vivo gene correction program and the safety, efficacy and delivery of our ARCUS genome editing technology. In some cases, you can identify forward-looking statements by terms such as anticipate, believe, could, expect, should, plan, intend, estimate, target, mission, may, will, would, should, could, target, project, predict, contemplate, potential, or the negative thereof and similar words and expressions.

Forward-looking statements are based on managements current expectations, beliefs and assumptions and on information currently available to us. Such statements are subject to a number of known and unknown risks, uncertainties and assumptions, and actual results may differ materially from those expressed or implied in the forward-looking statements due to various important factors, including, but not limited to, our ability to become profitable; our ability to procure sufficient funding and requirements under our current debt instruments; our limited operating history; the success of our programs and product candidates; our dependence on our ARCUS technology; the initiation, cost, timing, progress and results of research and development activities, preclinical or greenhouse studies and clinical or field trials; our or our collaborators ability to identify, develop and commercialize product candidates; our or our collaborators ability to advance product candidates into, and successfully complete, clinical or field trials; our or our collaborators ability to obtain and maintain regulatory approval of our product candidates, and any related restrictions, limitations and/or warnings in the label of an approved product candidate; the laws and regulatory landscape that will apply to our and our collaborators development of product candidates; our ability to achieve our anticipated operating efficiencies as we commence manufacturing operations at our new facility; delays or difficulties in enrolling patients in clinical trials; our ability to obtain and maintain intellectual property protection for our technology and any of our product candidates; potential litigation relating to infringement or misappropriate of intellectual property rights; if our product candidates do not work as intended or cause undesirable side effects the potential for off-target editing or other adverse events, undesirable side effects or unexpected characteristics associated with any of our product candidates; risks associated with applicable healthcare, data privacy and security regulations and our compliance therewith; the rate and degree of market acceptance of any of our product candidates; the success of our existing collaboration agreements; our ability to enter into new collaboration arrangements; public perception about genome editing technology and its applications; competition in the genome editing, biopharmaceutical, biotechnology and agricultural biotechnology fields; potential manufacturing problems associated with any of our product candidates; pending and potential liability lawsuits and penalties related to our technology, our product candidates; the outbreak of the novel coronavirus disease (COVID-19); our current and future relationships with third parties; our ability to effectively manage the growth of our operations; our ability to attract, retain, and motivate key scientific and management personnel; effects of natural or manmade disasters, public health emergencies and other natural catastrophic events; insurance expenses and exposure to uninsured liabilities; market and economic conditions; dilution and fluctuations in our stock price; and other important factors discussed under the caption Risk Factors in our Annual Report on Form 10-K for the fiscal year ended December 31, 2019, as supplemented by the risk factor contained in our Current Report on Form 8-K filed with the SEC on April 6, 2020, as any such factors may be updated from time to time in our other filings with the SEC, which are accessible on the SECs website atwww.sec.gov.

All forward-looking statements speak only as of the date of this press release and, except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

Investor Contacts:Nick RiddlePrecision BioSciencesTel. (919) 314-5512IR@precisionbiosciences.com

Josh RappaportStern Investor RelationsTel. (212) 362-1200josh.rappaport@sternir.com

Media Contact:Maurissa MessierPrecision BioSciencesTel. (919) 314-5512media@precisionbiosciences.com

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4THBIN Appoints Cynthia Salitsky as Chief Marketing Officer to Support Market Expansion and Drive Growth – PRNewswire

Wednesday, April 29th, 2020

Ms. Salitsky joins 4THBIN from The Chemours Company, where she held the role of Global Communications Director for Chemours' Fluoroproducts business and led crisis and issues communications for the company. During her tenure at Chemours, she was responsible for developing the company's strategic brand and marketing agenda for six of the company's seven power brands. Prior to joining Chemours, Ms. Salitsky spent twenty years with AstraZeneca, where she held numerous communication leadership roles, including Head of Enablement for Global R&D Communications,Head of Key Account Management and Communication Excellence, Global R&D and Director, R&D PR-Communication Strategy.Ms. Salitsky holds a Bachelor of Science degree in Genetic Engineering from Cedar Crest College and completed the Wharton Management Program at the University of Pennsylvania.

With over 25 years of experience, Ms. Salitsky has a unique blend of expertise in communications, sales and marketing, strategic planning as well as managerial and operational excellence. Her career is marked with critical roles in several 'start up' functions and capabilities within an organization, making her a perfect fit for 4THBIN.

"We are delighted to have someone of Cynthia's caliber and experience join our team," said Paul Kirsch, CEO and Co-founder of 4THBIN. "4THBIN has experienced exponential growth over the past couple of years, and Cynthia's experience will help us continue to expand our market reach and drive future growth."

"I couldn't be more excited to join such an amazing team that is truly passionate about making a difference and executing on its promise to deliver sustainable and secure e-recycling and data destruction solutions to today's leading industries," said Salitsky.

About 4THBIN

4THBIN is a certified and secure e-recycling solution provider to over 6,000 businesses from Fortune 100 companies to start-ups across the United States.We provide certified data destruction support to today's top industries and help them deliver on their corporate social responsibility commitments by ensuring their e-waste is sustainably and legally recycled. We are certified and accredited by the industry's most rigorous and trusted institutions for data security and sustainability.4THBIN was New York City's first company to be certified by e-Stewards and has received Evovadis' platinum rating, placing 4TBIN in the top 1% of their most responsible companies. For more information, we invite you to visit 4THBIN.comor follow ups on Twitter @4THBINor LinkedIN.

Media Contact:Kira Perdue[emailprotected]404-556-0062

SOURCE 4THBIN

http://www.4THBIN.com

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4THBIN Appoints Cynthia Salitsky as Chief Marketing Officer to Support Market Expansion and Drive Growth - PRNewswire

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The US already has the technology to test millions of people a day – MIT Technology Review

Wednesday, April 29th, 2020

There is widespread agreement that the only way to safely reopen the economy is through a massive increase in testing. The US needs to test millions of people per day to effectively track and then contain the covid-19 pandemic.

This is a tall order. The country tested only around 210,000 people per day last week, and the pace is not increasing fast enough to get to millions quickly.

The urgency to do better is overwhelmingly bipartisan, with the most recent legislation adding $25 billion for testing a few days ago. Fears are growing, however, that testing might not scale in time to make a difference. As Senators Lamar Alexander and Roy Blunt wrote last week, We have been talking with experts across the government and the private sector to find anyone who believes that current technology can produce the tens of millions of tests necessary to put this virus behind us. Unfortunately, we have yet to find anyone to do so.

We believe that it can be done. The scientific community has the technological capabilities today to test everyone who needs it and enable people to come back to work safely.

To be clearthe senators are right that simply scaling up current practices for covid testing is insufficient. However, with a bit of innovation, the US can meet the need without inventing entirely new technologies. The necessary scale can be achieved by deploying the fruits of the last decade of innovation in biology, including the dizzying advances in DNA sequencing, genetic engineering, industrial automation, and advanced computation.

We speak from experience. We have worked with and helped engender many of these technologies across academia and industry. Scaling them for widespread testing will require investment, infrastructure, and determination, but nothing technologically or logistically infeasible.

Tests for mass screening may have different requirements and characteristics from the tests run in clinical labs today that are approved by the Food and Drug Administration. So what might a solution look like?

It must be scalable, meaning tens or hundreds of thousands of tests per day per facility, or at-home tests. It must be sensitive to early stages of infection, detecting the actual virus rather than immunity to it. And it must be less bound by health insurance and regulatory constraints, to allow fast and broad testing, contact tracing, and isolation. These differences do not mean lower standards. In fact, screening at this scale will require stringent requirements for safety, accuracy, and reliability.

The life sciences community is rising to the challenge. We are repurposing our labs to advance new centralized and at-home methods that solve the bottlenecks preventing testing from reaching global scale. This community is moving fast, with shared purpose and a commitment to open collaboration. As a result of these efforts, several promising avenues are emerging.

Some rely on DNA sequencing tools that have improved a million-fold since the completion of the Human Genome Project nearly 20 years ago. Not only can these tools now read trillions of base pairs of human DNA every day, but they can be readily repurposed to test for the presence of coronavirus at mass scale, using instruments that already exist across the country. Some methods, such as SHERLOCK and DETECTR, harness CRISPR DNA and RNA recognition tools to enable rapid, distributed testing in doctors offices and at other sites. Other efforts are removing critical bottlenecks, such as sample purification, to make the existing approaches more scalable.

There are additional possibilities, and the US needs to place bets on several of them at the same time. Some of those bets might fail, but the severity of the moment requires that we try. Chances are, we will need more than one of them.

As important as the diagnostic technology itself is the need to fuel innovation at all stages of the testing process, including sample collection, regulation, logistics, manufacturing, distribution, scale-up, data infrastructure, and billing. These are solvable problems. The solutions may sometimes differ from current clinical testing conventions, but these are not conventional times.

Maybe cotton swabs or saliva can be used for collection rather than traditional nasopharyngeal swabs, which are in critically short supply. Maybe mass screening tests dont have to have the tested persons name and date on every collection tube but could instead include a bar code that you snap a picture of with your phone. Maybe these tests can be self-administered at home or work rather than conducted by trained professionals in clinical settings. Maybe samples from low-risk, asymptomatic people can be pooled together for initial testing and further screened only in the event of a positive result. This would allow many more samples to be analyzed at once.

State or federal regulatory agencies could make these adjustments to conventional practices more easily if they were willing to treat mass screening for bringing people back to work differently from the testing used in clinical settings. In addition, mass screening efforts will require unconventional partnerships with private companies, nonprofits, universities, and government agencies to support the logistics, collection, manufacturing, scale-up, and data infrastructure to make such a system possible. All this can be done, and some of it is already starting to be donebut we must not lose hope.

The United States capabilities in the life sciences and information technology are unmatched in the world. The time is now to rapidly build a massively scaled screening program that will save lives while allowing us to reopen our economy and keep it open. This can be done, but it will require urgency and determination to make multiple, simultaneous bets on infrastructure, regulation, and technology, as well as collaboration to put it all together.

We have united before to face far greater challenges as a nation, and we can do so again.

Sri Kosuri is cofounder and CEO of Octant and an associate professor in the Department of Chemistry and Biochemistry at UCLA. Feng Zhang is the James and Patricia Poitras Professor of Neuroscience at MITs McGovern Institute, a core member of the Broad Institute, a Howard Hughes Medical Institute Investigator, and cofounder of Sherlock Biosciences. Jason Kelly is cofounder and CEO of Ginkgo Bioworks. Jay Shendure is a Howard Hughes Medical Institute Investigator at the University of Washington School of Medicine and scientific director of the Brotman Baty Institute.

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The Controversial Experiments and Wuhan Lab Suspected of Starting the Coronavirus Pandemic – Newsweek

Wednesday, April 29th, 2020

Just one day after the U.S. surpassed China to become the country with the highest number of Covid-19 cases, the U.S. Defense Intelligence Agency updated its assessment of the origin of the novel coronavirus to reflect that it may have been accidentally released from an infectious diseases lab, Newsweek has learned.

The report, dated March 27 and corroborated by two U.S. officials, reveals that U.S. intelligence revised its January assessment in which it "judged that the outbreak probably occurred naturally" to now include the possibility that the new coronavirus emerged "accidentally" due to "unsafe laboratory practices" in the central Chinese city of Wuhan, where the pathogen was first observed late last year. The classified report, titled "China: Origins of COVID-19 Outbreak Remain Unknown," ruled out that the disease was genetically engineered or released intentionally as a biological weapon.

"We have no credible evidence to indicate SARS-CoV-2 was released intentionally or was created as a biological weapon," the report found. "It is very unlikely that researchers or the Chinese government would intentionally release such a dangerous virus, especially within China, without possessing a known and effective vaccine." Every scientist interviewed by Newsweek for this story also rejected categorically the notion that the virus was intentionally released.

Covid-19 has infected nearly 3 million people across the globe, initially ravaging China before hitting hardest in the West and leaving the United States as the most deeply-afflicted country, with more than 55,000 deaths as of April 27. Its origin remains the subject of not only scientific debate, but a politically charged dispute in the international community.

Citing academic literature, the DIA document states that a "definitive answer may never be known" as to how the disease truly first emerged. A U.S. intelligence spokesperson told Newsweek, "the Intelligence Community has not collectively agreed on any one theory."

Uncertain source

Tracing the origin of a new virus is not easy. It took researchers at the Wuhan Institute more than a decade to trace the 2002-2003 SARS virus to remote bat caves in Yunnan province. It's not surprising, then, that in early February, China's Academy for Military Medical Sciences "concluded that it was impossible for them to scientifically determine whether the Covid-19 outbreak was caused naturally or accidentally from a laboratory incident," according to the DIA document.

Initial assessments conducted by the Chinese government pointed to the city's Huanan Seafood Market as the likely cause of a natural outbreak of SARS-CoV-2, a new coronavirus that causes Covid-19. In the early days of the outbreak, local officials played down the possibility of human-to-human transmission of the virus and silenced doctors who spoke out about the growing outbreak. It may have undercounted deaths and the number of cases of Covid-19. A spurious theory that the U.S. deliberately planted the virus in Wuhan also started circulating.

China's foreign ministry told reporters April 23rd that the World Health Organization found "no evidence" the outbreak started at the Wuhan laboratory, and Yuan Zhiming, vice president of the Wuhan Institute of Virology and president of the Chinese Academy of Sciences Wuhan Branch, blasted the inference of intentional misuse or creation as "malicious" and "impossible."

"The director of the Galveston National Laboratory in the United States made it clear that our laboratory is just as well managed as labs in Europe and the U.S.," he said. "I think it is understandable for people to make that association. But it is a malicious move to purposefully mislead the people" to think that the virus escaped from [our Wuhan] labs.

"They have no evidence or logic to support their accusations. They are basing it completely on their own speculations."

The DIA report, however, cites U.S. government and Chinese researchers that found "about 33 percent of the original 41 identified cases did not have direct exposure" to the market. That, along with what's known of the laboratory's work in past few years, raised reasonable suspicion that the pandemic may have been caused by a lab error, not the wet market.

Here's what the scientific and circumstantial evidence shows.

Back in 2002, when SARS emerged in China's Guandong province, it served as a wake-up call. Over the next few decades, the U.S., China and other nations poured money into efforts to hunt down and catalogue strange new pathogens that live in wild animals and figure out how much of a threat they pose to humans, with the goal of preventing the next devastating pandemic.

In the fall of 2019, the SARS-CoV-2 coronavirus emerged in the middle of the large, cosmopolitan city of Wuhan. Chinese officials at first insisted that the virus, SARS-CoV-2, could be caught only through direct contact with animals. But many of the early patients in Wuhan had no connection to the wild animal markets, which meant that the virus had already been spreading from person to person. When this fact came out, it cast doubt on the veracity of information coming from China, but the virus was well on its way to becoming a deadly pandemic.

In the early days, the prevailing theory of the virus' origins was that it, like SARS, arose in bats, passed to some other mammal such as a pangolin, and ultimately entered the population through the wild-animal markets.

By March, the wild-virus theory was still the most likely explanation of the origin of SARS-CoV-2--but it was starting to look a little ragged around the edges. For one thing, the Wuhan Institute of Virology, not far from the animal markets in downtown Wuhan, houses the world's largest collection of coronaviruses from wild bats, including at least one virus that bears a resemblance to SARS-CoV-2. What's more, Wuhan Institute of Virology scientists have for the past five years been engaged in so-called "gain of function" (GOF) research, which is designed to enhance certain properties of viruses for the purpose of anticipating future pandemics. Gain-of-function techniques have been used to turn viruses into human pathogens capable of causing a global pandemic.

This is no nefarious secret program in an underground military bunker. The Wuhan lab received funding to do this work in part from a ten-year, $200 million international program called PREDICT, funded by the U.S. Agency for International Development and other countries. Similar work, funded in part by the U.S. National Institutes of Health, has been carried out in dozens of labs throughout the world. Some of this research involves taking deadly viruses and enhancing their ability to spread quickly through a populationresearch that took place over the objections of hundreds of scientists, who have warned for years of the program's potential to cause a pandemic.

In the years since the SARS outbreak, many instances of mishaps involving the accidental release of pathogens have taken place in labs throughout the world. Hundreds of breaches have occurred in the U.S., including a 2014 release of anthrax from a U.S. government lab that exposed 84 people. The SARS virus escaped from a Beijing lab in 2004, causing four infections and one death. An accidental release is not complicated and doesn't require malicious intent. All it takes is for a lab worker to get sick, go home for the night, and unwittingly spread the virus to others.

The Wuhan Institute has a record of shoddy practices that could conceivably lead to an accidental release, as officials at the U.S. Embassy in Beijing reportedly warned in a cable on January 19, 2018. "During interactions with scientists at the WIV laboratory, they noted the new lab has a serious shortage of appropriately trained technicians and investigators needed to safely operate this high-containment laboratory," states the cable, according to the Washington Post.

To be sure, there's no evidence that SARS-Cov-2 came from the Wuhan lab, nor that the virus is the product of engineering. Most scientists believe, based on the evidence available, that a natural origin is the most likely explanation. But neither have they ruled out these possibilities. "At this stage, it is not possible to determine precisely the source of the virus which caused the COVID-19 pandemic," says the World Health Organization in a statement to Newsweek. "All available evidence suggests that the virus has a natural animal origin and is not a manipulated or constructed virus."

The circumstantial evidence is strong enough to warrant putting the lab's programs and practices at the heart of the investigation. And it's worth looking anew at whether scientists, in their efforts to protect the public from the threat of natural pathogens, overreached.

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Animal Passage

Ten years ago, the viral pathogen most in the news was not a coronavirus but influenzain particular, a strain of flu, designated H5N1, that arose in birds and killed a high proportion of those who were infected. For a while, the virus made headlines. Then it became clear that nearly everyone who caught the bird-flu virus got it directly from handling birds. To cause a plague, it's not enough that a virus is an efficient killer. It also has to pass easily from one person to the next, a quality called transmissibility.

Around this time, Ron Fouchier, a scientist at Erasmus University in Holland, wondered what it would take for the bird flu virus to mutate into a plague virus. The question was important to the mission of virologists in anticipating human pandemics. If H5N1 were merely one or two steps away from acquiring human transmissibility, the world was in danger: a transmissible form of H5N1 could quickly balloon into a devastating pandemic on the order of the 1918 flu, which killed tens of millions of people.

To answer the question, scientists would have to breed the virus in the lab in cell cultures and see how it mutated. But this kind of work was difficult to carry out and hard to draw conclusions from. How would you know if the end result was transmissible?

The answer that Fouchier came up with was a technique known as "animal passage," in which he mutated the bird-flu virus by passing it through animals rather than cell cultures. He chose ferrets because they were widely known as a good stand-in for humansif a virus can jump between ferrets, it is likely also to be able to jump between humans. He would infect one ferret with a bird-flu virus, wait until it got sick, and then remove a sample of the virus that had replicated in the ferret's body with a swab. As the virus multiplies in the body, it mutates slightly, so the virus that came out of the ferret was slightly different from the one that went into it. Fouchier then proceeded to play a version of telephone: he would take the virus from the first ferret and infect a second, then take the mutated virus from the second ferret and infect a third, and so on.

After passing the virus through 10 ferrets, Fouchier noticed that a ferret in an adjacent cage became ill, even though the two hadn't come into contact with one another. That showed that the virus was transmissible in ferretsand, by implication, in humans. Fouchier had succeeded in creating a potential pandemic virus in his lab.

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When Fouchier submitted his animal-passage work to the journal Science in 2011, biosecurity officials in the Obama White House, worried that the dangerous pathogen could accidentally leak from Fouchier's lab, pushed for a moratorium on the research. Fouchier had done his work in BSL-2 labs, which are intended for pathogens such as staph, of moderate severity, rather than BSL-4, which are intended for Ebola and similar viruses. BSL-4 labs have elaborate safeguardsthey're usually separate buildings with their own air circulation systems, airlocks and so forth. In response, the National Institutes of Health issued a moratorium on the research.

What followed was a fierce debate among scientists over the risks versus benefits of the gain-of-function research. Fouchier's work, wrote Harvard epidemiologist Marc Lipsitch in the journal Nature in 2015, "entails a unique risk that a laboratory accident could spark a pandemic, killing millions."

Lipsitch and 17 other scientists had formed the Cambridge Working Group in opposition. It issued a statement pointing out that lab accidents involving smallpox, anthrax and bird flu in the U.S. "have been accelerating and have been occurring on average over twice a week."

"Laboratory creation of highly transmissible, novel strains of dangerous viruses... poses substantially increased risks," the statement said. "An accidental infection in such a setting could trigger outbreaks that would be difficult or impossible to control. Historically, new strains of influenza, once they establish transmission in the human population, have infected a quarter or more of the world's population within two years." More than 200 scientists eventually endorsed the position.

The proponents of gain-of-function research were just as passionate. "We need GOF experiments," wrote Fouchier in Nature, "to demonstrate causal relationships between genes or mutations and particular biological traits of pathogens. GOF approaches are absolutely essential in infectious disease research."

The NIH eventually came down on the side of Fouchier and the other proponents. It considered gain-of-function research worth the risk it entailed because it enables scientists to prepare anti-viral medications that could be useful if and when a pandemic occurred.

By the time NIH lifted the moratorium, in 2017, it had granted dozens of exceptions. The PREDICT program, started in 2009, spent $200 million over 10 years, sending virologists all over the world to look for novel viruses and perform gain-of-function research on them. The program's funding ran out in 2018 and it wasn't renewed. Early this year, after the Trump administration drew criticism for canceling the program, it granted a six-month extension.

By the time the current pandemic hit, animal-passage experiments had become commonplace. Scientists in many of the more than 30 BSL-4 labs around the world had used them to enhance the transmissibility of respiratory-tract pathogens.

Did the work help during the current pandemic? In a recent article in the Lancet, Colin Carlson, an expert in emerging infectious diseases at Georgetown University, argued that work funded by PREDICT helped virologists rapidly isolate and classify the SARS-CoV-2 virus when it came out. However, the research "could have been better positioned for an overall impact." Although the program found hundreds of new viruses, it's nearly impossible for scientists to assess their risk to humans. The only way to tell is to "observe a human infection."

Richard Ebright, an infectious disease expert at Rutgers, put it more bluntly. "The PREDICT program has produced no resultsabsolutely no resultsthat are of use for preventing or combating outbreaks. There's no information from that project that will contribute in any way, shape or form to addressing the outbreak at hand. The research does not provide information that's useful for developing antiviral drugs. It does not provide information that's useful for developing vaccines."

China's role

The Wuhan Institute of Virology is one of many labs to receive PREDICT funding. Shi Zheng-Li, a virologist known as "bat woman" for her group's work in collecting hundreds of coronaviruses, and her staff at the Institute explored the same bat caves that were thought to have given rise to the original SARS virus in 2002. Her scientists penetrated remote caves, swabbing bats' anuses and collecting their excretions. When they returned to the lab, they cultured the viruses they found, determined their genomic sequences and tried to determine how they infect cells and animals in the lab.

The Institute began a program of gain-of-function research into bat coronaviruses in 2015. That involved taking selected strains and seeking to increase the ability of those viruses to transmit from one person to another. The gain-of-function research went hand-in-hand with the surveillance project. As scientists identified new classes of bat viruses that have the ability to infect human cells, that raised the question of what changes would have to arise in nature to make that virus transmissible in humans, which would pose a pandemic threat.

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In 2015, the Wuhan lab performed a gain of function experiment using cut-and-paste genetic engineering, in which scientists take a natural virus and directly make substitutions in its RNA coding to make it more transmissible. They took a piece of the original SARS virus and inserted a snippet from a SARS-like bat coronavirus, resulting in a virus that is capable of infecting human cells. A natural virus altered with these methods would be easily flagged in a genetic analysis, like a contemporary addition to an old Victorian house.

A virus produced with animal passage methods would be much harder to spot. These viruses are not directly manipulated. When the virus passes from one animal to the next, it undergoes something similar to what would happen in the wild during the course of its evolution. A wild coronavirus passed through 10 ferrets would be difficult to identify as having been engineered or manipulated.

There is no published record of animal-passage work on coronaviruses in the Wuhan Institute. The lab got its first BSL-4 lab in 2018, which is now considered a requirement for this kind of work (though some work proceeds in BSL-3-enhanced labs). It's possible that researchers started animal passage work in the BSL-4 lab but didn't finish it in time to publish before the current pandemic, when China tightened up on publications. It's possible that the work was done in secret. It's possible that it never happened at all. But some scientists think it's unlikely that an expensive BSL-4 lab would not be doing animal-passage research, which by 2018 was not unusual.

Tracing the origins

To figure out where SARS-CoV-2 came from, Kristian Andersen of Scripps Research and his colleagues performed a genetic analysis: they published the work, which has been widely cited, on March 17 in Nature Medicine. The researchers focused on certain genetic features of the virus for telltale signs of "manipulation."

One feature was the spike of protein that the virus uses to attach so effectively to the human body's ACE2 receptors, a molecular feature of the cells in our lungs and other organs. The spike in SARS-Cov-2, the authors conclude, differs from that of the original SARS virus in ways that suggest it was "most likely the product of natural selection"in other words, natural, not manipulated in a lab.

However, the paper's reasoning as to why animal passage, in particular, can be ruled out, is not clear. "In theory, it is possible that SARS-CoV-2 acquired the... mutations during adaptation to passage in cell culture," the authors write. The theory that the virus mutated in mammalian hosts such as pangolins "provides a much stronger... explanation." Whether or not that includes animal passage in a lab, they don't say. Andersen didn't respond to Newsweek requests for comment.

Rutger's Ebright, a longtime opponent of gain of function research, says that the Andersen analysis fails to rule out animal-passage as an origin of SARS-CoV-2. "The reasoning is unsound," he wrote in an email to Newsweek. "They favor the possibility 'that the virus mutated in an animal host such as a pangolins' yet, simultaneously, they disfavor the possibility that the virus mutated in 'animal passage.' Because the two possibilities are identical, apart from location, one can't logically favor one and disfavor the other."

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Jonathan Eisen, an evolutionary biologist at UC Davis, says that the preponderance of evidence, while not definitive, suggests that the virus came from nature, not a lab. "There's no hint there that there's something unnatural, that is, genetically engineered," he says. But "there is some wiggle room" in the findings that admits the possibility that the virus was concocted in a lab via animal passage. "Passaging is hard to test for. Escape from a lab is hard to test for," he says. "If [Wuhan researchers] collected something from the field and they were doing some experiments in the lab with it, and some person got infected and then it spread from there, that would be really hard to distinguish from it having spread in the field directly."

Wuhan is in possession of a virus, RATG13, that is thought to be the most similar to SARS-CoV-2 of any known virusthe two share 96 percent of their genetic material. That four-percent gap would still be a formidable gap for animal-passage research, says Ralph Baric, a virologist at the University of North Carolina who collaborated with Shi Zheng-Li on the 2015 gain-of-function research. "You keep running into problems that just don't make it likely," he says. Wuhan would probably have had to start with a virus closer to SARS-CoV-2 than RATG13, which is within the realm of possibilities.

"The only way to resolve it," says Baric, "is transparency and open science and have some real investigation into it. I don't think the Chinese are going to allow that. I don't know what any country would do in this situation. I would like to think that the U.S. would be transparent."

Jenni Fink contributed to this report

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Apic Bio Announces Presentations at the American Society of Gene and Cell Therapy’s 23rd Annual Meeting – BioSpace

Wednesday, April 29th, 2020

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Apic Bio Inc., an innovative gene therapy company developing novel treatment options for patients with rare genetic diseases, today announced that it will have three poster presentations at the American Society of Gene and Cell Therapys 23rd Annual Meeting taking place May 12-15, 2020 in virtual format. Posters will be available at http://www.asgct.org.

The posters include:

Abstract Title: High Efficiency Downstream Processing and Enrichment of Full AAV Particles Produced from Suspension HEK293 Cells (abstract #467)Presenter: Scott Loiler, Chief Technology Officer, Apic BioSession Title: Vector and Cell Engineering, Production or ManufacturingDate/Time: Tuesday May 12, 2020 5:30 PM to 6:30 PM ET

Abstract Title: Optimizing Suspension HEK293 Transfection Processes for AAV Productivity (abstract #859)Presenter: Scott Loiler Chief Technology Officer, Apic BioSession Title: Vector and Cell Engineering, Production or ManufacturingDate/Time: Wednesday May 13, 2020 5:30 PM to 6:30 PM ET

Abstract Title: Bridging Efficacy Data in an ALS Mouse Model with Clinical Route of Administration in Nonhuman Primates to Derive a Meaningful Clinical Dose Range (abstract #1114)Presenter: Randal Hand, Senior Scientist, Apic BioSession Title: Neurological DiseasesDate/Time. Thursday May 14, 2020 5:30 PM to 6:30 PM ET

About Apic Bio

Apic Bio is an innovative gene therapy company focused on developing first-in-class treatment options for rare, undertreated neurological and liver diseases. The Company's lead program is an adeno-associated (AAV)-based gene therapy for the treatment of the copper zinc superoxide dismutase 1 (SOD1) genetic form ALS. Preclinical studies of additional genetic forms of ALS (C9Orf72) and Alpha-1 Antitrypsin Deficiency (Alpha-1) are ongoing. The Company is also advancing discovery programs for two undisclosed CNS indications that leverage its proprietary silence and replace THRIVE platform. The Company is backed by leading and disease-centric investors, including Morningside Ventures, ALS Investment Fund, and The Alpha-1 Project (TAP). For more information please visit http://www.apic-bio.com.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200428006046/en/

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Researchers race to find a vaccine for COVID-19 – Scot Scoop News

Wednesday, April 29th, 2020

As COVID-19 continues to rage across the U.S., scientists all over the world race to find a vaccine.

Researchers are currently testing vaccines made from genetic engineering along with the traditional vaccine, composed of the inactive virus.

A laboratory at Oxford University is preparing to begin a 6,000-person trial sometime next month, gaining a significant head start in the race to find a vaccine. Oxfords Jenner Institute performed similar inoculations for other strains of the virus last year and was able to begin scheduling tests to prove if the vaccine works.

Oxford scientists said the vaccine could have the first few million doses ready by September with regulators emergency approval, according toThe New York Times.

Another research institute, Sinovac Biotech, based in Beijing, created a trial vaccine consisting of an inactive strain of the virus and began testing on eight monkeys, and they saw no apparent side effects. They then introduced an active strain of the virus into the monkeys lungs and found that none of the monkeys developed a full infection.

However, according toScience Magazine Online, the testing group may have been too small to show results accurately, and other researchers from the University of Pittsburgh believe the way the virus stock was grown may have altered the study.

Its still too early to define the best model for studying COVID-19, a researcher at Sinovac Biotech said.

As scientists and researchers band together to find a vaccine, the effects and outcomes are still unknown, and many researchers stress that there is no promise of success with any of the current trials.

Sean Doyle, a 31-year-old medical student at Emory School of Medicine, volunteered to be one of the first people to test a vaccine. Doyle volunteered to test the vaccine on himself despite there being little known about the side effects or possible risks it could cause.

With this vaccine, no one knows what the chances are, but the potential risks are outweighed by the potential benefits of the vaccine for me. Right now, there are no great preventative measures for containing the virus, Doyle said in an interview with CNN.

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400 reads: What workers on the front line are reading – Forsyth County News Online

Wednesday, April 29th, 2020

See the full issue of the May 400 Life magazinehere.

The year 2020 has presented our county, country, and world with circumstances we were not expecting. Local residents have demonstrated a resiliency and perseverance that exemplify the true merits of our community. Many of us have been relegated to our homes, but there are those that work on the front lines, providing essential services and support. I reached out to five of my friends who continue to meet the needs of our community. Each of these accomplished women selected one book to share and we hope that these recommendations will bring you some escape and enjoyment as we continue to live our lives through this historical period. -By Becky Cahill

My book recommendation is Evvie Drake Starts Over by Linda Holmes. It is a charming novel about a recently widowed Evvie, who lives in Maine and keeps to herself after her husband passes away unexpectedly. One of her best friends, Andy, worries about her grieving and invites his childhood friend, Dean, a former major-league pitcher struggling with a case of the yips to come and live in the apartment behind Evvies house. The development of this storyline made this book an enjoyable read for me. The characters are easy to love and there is a hint of romance but its the realistic kind, with imperfect people navigating their own heartaches and perceptions of themselves. Its a warm story about friendship and finding love in unexpected ways. You only read a good book for the first time once and Evvie Drake Starts Over is a great book I never wanted to put down.

My favorite book just so happens to be a childrens book, which should come to no surprise considering my profession. Its called Love You Forever by Robert Munsch. The book is about the love a mom has for her child no matter how old they get. It begins with the mom caring for her newborn son. Every night she enters his room while he is sleeping and sings, Ill love you forever, Ill like you for always, as long as Im living, my baby youll be. She continues to sneak into his room all the way into adulthood singing the same song. One day, she is old and can no longer go into his room to sing this song. The story ends with him sneaking into his mothers room, wrapping her old frail body up into his arms, and singing, Ill love you forever, Ill like you for always, as long as Im living, my mommy youll be. I love this book because it pulls at the heart strings, and it depicts the love between a mother and child perfectly.

Behind Closed Doors by B.A. Paris is one of my all-time favorite books. In what seems to be the perfect marriage, a woman is actually held prisoner by her dashing husband. The main character, Grace, thought her life would revolve around the care of her younger sister, Millie, who has Down syndrome. She didnt expect to be swept off her feet by Jack Angel, a charming man who spoils Millie as much as he seems to love Grace. After a whirlwind courtship, Grace and Jack get married, though the wedding doesnt go smoothly, with Millie tumbling down the stairs hours before the ceremony and breaking her leg. It isnt until the couple is away on their honeymoon that the first signs of something wrong in the relationship start to show. When Millie is planning to come live with the couple, Grace schemes a way to escape Jacks clutches and save Millie from the same fate. You wont be able to put this book down to see how it ends!

Prey by Michael Crichton is a cautionary novel about advancements in nanotechnology, genetic engineering, and artificial intelligence. In Prey, an experiment has gone wrong. A cloud of nanoparticles escapes from a lab and is self-sustaining and self-reproducing. Initially programmed as imagining technology for military use, the scientists give the nanoparticles a bacterial agent to provide them the ability to work together towards a set goal. It becomes more intelligent and begins to learn from experience. The nanoparticles swiftly become a predator and become more deadly with every hour. The scientists must fight for survival and come up with a plan to eliminate the swarm. I have always been fascinated with science and technological advancements. This book catches your attention and keeps you eager to turn each page. This book is thrilling but also educational. Learning through fiction is an engaging way to pick up knowledge. The action and mystery of Prey, as well as the entertainment of the story, makes this one of my favorite books.

Published posthumously, Ill Be Gone in the Dark: One Womans Obsessive Search for the Golden State Killer details true crime author Michelle McNarmas journey to discover the identity of the Golden State Killer. The book is meticulous in the best way; Michelle provides detailed maps, victim statements, and interviews with former and current investigators. As a corporate security professional, it was fascinating to compare law enforcement investigation tactics from the beginning of the killers crime spree to present day. I was also drawn in by Michelles vulnerability, as she doesnt shy away from how the case impacted her own psyche (she notes there is a scream permanently lodged in my throat). A thoughtful, compelling work, Ill Be Gone in the Dark represents the future of true crime writing.

Becky Cahill is a career educator and an avid reader. She reads extensively in her free time and tracks her favorites (and those that arent even close)on her blog at tobereadlist.home.blog. Becky is the host of Read It or Leave It! a weekly reading podcast available on Apple Podcasts and Spotify.

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Intellia Therapeutics to Present New Preclinical Data from Its CRISPR/Cas9 Programs at the 23rd Annual Meeting of the American Society of Gene and…

Wednesday, April 29th, 2020

CAMBRIDGE, Mass., April 28, 2020 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology bothin vivoandex vivo,announced that five abstracts were accepted for the 23rd Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), taking place virtually from May 12-15, 2020. Abstracts are available on the ASGCT website.

Intellias data include important updates about the companys progress and platform development activities:

Oral Presentations

Enhanced tgTCR T Cell Product Attributes Through Process Improvement of CRISPR/Cas9 EngineeringAs a follow-on to data presented at Keystone Symposias Engineering the Genome Conference this past February, Intellias ASGCT presentation will focus on process improvements in its CRISPR/Cas9-based engineering to deliver T cell therapies with high levels of editing, achieving robust levels of expansion, desirable memory phenotypes, improved function and reduced translocations. These platform advances support NTLA-5001, which is Intellias first wholly owned engineered T cell therapy development candidate. NTLA-5001 utilizes a T cell receptor (TCR)-directed approach to target the Wilms Tumor 1 (WT1) antigen, obtained through the ongoing research collaboration with IRCCS Ospedale San Raffaele, which is over-expressed in many hematologic and solid tumors. Intellia will focus its initial clinical investigation of NLTA-5001 on acute myeloid leukemia (AML), while exploring in ongoing preclinical studies its application in solid tumors. Intellia plans to submit an IND for NTLA-5001 for the treatment of AML in the first half of 2021.

Presenter: Aaron Prodeus, Ph.D., senior scientist, Cell TherapyAbstract number: 35Session: CAR T-Cell Therapies IPresentation date/time: Tuesday, May 12, 2020, from 11:45 a.m.-12 p.m. ET

Exploiting CRISPR-Genome Editing and WT1-Specific T Cell Receptors to Redirect T Lymphocytes Against Acute Myeloid LeukemiaThis presentation will focus on Intellias ongoing research collaboration with IRCCS Ospedale San Raffaele to apply CRISPR/Cas9 technology to develop engineered T cell therapies to address intractable cancers, such as AML. Researchers will also present data showing a significant decrease in AML tumor burden in mice treated with the WT1-specific TCRs, which are incorporated into Intellias lead NTLA-5001 candidate for the treatment of AML.

Presenter: Eliana Ruggiero, Ph.D., Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, ItalyAbstract number: 78Session: CAR T and Other Engineered T Cells Targeting Hematological MalignanciesPresentation date/time: Tuesday, May 12, 2020, from 3:45-4 p.m. ET

CRISPR/Cas9-Mediated Gene Knockout of KLKB1 to Treat Hereditary AngioedemaIntellia will present data updates on its potential hereditary angioedema (HAE) therapy, which uses the companys modular lipid nanoparticle (LNP)-based CRISPR/Cas9 delivery system to knock out the prekallikrein B1 (KLKB1) gene and reduce kallikrein activity. HAE is a rare genetic disorder characterized by recurring and unpredictable severe swelling attacks in various parts of the body, and is significantly debilitating or even fatal in certain cases. This presentation will include results from the companys ongoing collaboration with researchers at Regeneron and also will build on initial data released at Keystone Symposias Engineering the Genome Conference in February. Intellia expects to nominate a development candidate for HAE in the first half of 2020.

Presenter: Jessica Seitzer, director, GenomicsAbstract number: 1320Session: Gene Regulation and Delivery TechnologiesPresentation date/time: Friday, May 15, 2020, from 10:30-10:45 a.m. ET

Poster Presentations

Validation of CRISPR/Cas9 Off-Target Discovery Profiles from In Silico Prediction, Cell-Based and Biochemical-Based Assays with Targeted Off-Target SequencingThis presentation will highlight Intellias approach to assess off-target activity to identify highly specific CRISPR/Cas9 guides. Researchers demonstrated that potential off-target editing profiles discovered through empirical data from biochemical approaches were the most sensitive and accurate.

Presenter: Nishit Patel, Ph.D., senior associate scientist, Informatics, Computational Biology and GenomicsAbstract number: 203Session date/time: Tuesday, May 12, 2020, from 5:30-6:30 p.m. ET

In Vivo Model Development for Genome-Edited T Cell Therapeutics

Researchers will present improved murine models used to assess safety, efficacy and persistence of therapeutic modalities in cell-based therapies. Together with biotechnology company Taconic Biosciences, Intellia developed two in vivo mouse models, which allow for enhanced monitoring of graft-versus-host disease and human natural killer cytotoxicity.

Presenter: Yong Zhang, Ph.D., principal scientist, Cell TherapyAbstract number: 1174Session date/time: Thursday, May 14, 2020, from 5:30-6:30 p.m. ET

Workshop and Symposia

Building a Modular CRISPR/Cas9 Platform for Human Therapeutic ApplicationsIntellia will participate in the ASGCT Translational Science Genome Editing Pre-Meeting Workshop, which will include an overview on important factors to consider in building a modular CRISPR/Cas9 platform for human therapeutic applications.

Presenter: Jessica Seitzer, director, GenomicsSession: Gene Editing WorkshopPresentation date/time: Monday, May 11, 2020, from 4:10-4:30 p.m. ET

Industry Sponsored Symposia

Intellia will participate in an industry lunchtime panel discussion during ASGCT.

Panelist: Laura Sepp-Lorenzino, Ph.D., chief scientific officerPanel date/time: Wednesday, May 13, 2020, from 12-1:30 p.m. ET

About Intellia Therapeutics

Intellia Therapeuticsis a leading genome editing company focused on developing proprietary, curative therapeutics using the CRISPR/Cas9 system. Intellia believes the CRISPR/Cas9 technology has the potential to transform medicine by permanently editing disease-associated genes in the human body with a single treatment course, and through improved cell therapies that can treat cancer and immunological diseases, or can replace patients diseased cells. The combination of deep scientific, technical and clinical development experience, along with its leading intellectual property portfolio, puts Intellia in a unique position to unlock broad therapeutic applications of the CRISPR/Cas9 technology and create a new class of therapeutic products. Learn more aboutIntellia Therapeuticsand CRISPR/Cas9 atintelliatx.comand follow us on Twitter @intelliatweets.

Forward-Looking Statements

This press release contains forward-looking statements of Intellia Therapeutics, Inc. (Intellia or the Company) within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, but are not limited to, express or implied statements regarding Intellias ability to advance and expand the CRISPR/Cas9 technology to develop human therapeutic products that meet the regulatory requirements in the relevant jurisdictions, as well as our CRISPR/Cas9 intellectual property portfolio; our ability to achieve stable or effective genome editing; our ability to effectively administer one dose or multiple doses of our CRISPR/Cas9 product candidates; the potential timing and advancement of our preclinical studies, including non-human primate studies for our transthyretin amyloidosis (ATTR) program (NTLA-2001) and our hereditary angioedema (HAE) program, and other studies for these and other programs, including preclinical and human clinical trials; the ability to demonstrate our platforms modularity and replicate or apply results achieved in our preclinical studies, including those in our ATTR, HAE and Wilms Tumor 1 (WT1")/acute myeloid leukemia (AML) programs or research projects, in any future studies, including human clinical trials; our ability to generate data and replicate results relating to enhancements to our proprietary lipid nanoparticle (LNP) technology, including its formulation and components, in preclinical or clinical studies, or that any enhancements will result in an improved product candidate profile; the potential development of other in vivo or ex vivo cell therapeutics of all types, and those targeting WT1 in particular, using CRISPR/Cas9 technology; our plans to submit an IND application for NTLA-2001 for ATTR in the second half of 2020, as well as for NTLA-5001, our first T cell receptor (TCR)-directed engineered cell therapy development candidate for our AML program in the first half of 2021; our plans to nominate a development candidate for our HAE program in the first half of 2020; our expectations regarding potential patient populations that may be addressed by each of our programs; actions by government agencies; our growth as a company and the anticipated contribution of the members of our board of directors and our executives to our operations and progress; the impact of our collaborations on our research and development programs; the potential timing of regulatory filings regarding our development programs; the potential commercial opportunities, including value and market, for our product candidates; our expectations regarding our use of capital and other financial results during 2020; and our ability to fund operations through the end of 2021.

Any forward-looking statements in this press release are based on managements current expectations and beliefs of future events, and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to Intellias ability to protect and maintain its intellectual property position; risks related to Intellias relationship with third parties, including its licensors and licensees; risks related to the ability of its licensors to protect and maintain their intellectual property position; uncertainties related to the initiation and conduct of studies and other development requirements for its product candidates; the risk that any one or more of Intellias product candidates will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; and the risk that Intellias collaborations with Regeneron, OSR or its other collaborations will not continue or will not be successful. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Intellias actual results to differ from those contained in the forward-looking statements, see the section entitled Risk Factors in Intellias most recent annual report on Form 10-K as well as discussions of potential risks, uncertainties, and other important factors in Intellias other filings with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and Intellia undertakes no duty to update this information unless required by law.

Intellia Contacts:

Media:

Lynnea Olivarez

Director

External Affairs & Communications

+1 956-330-1917

lynnea.olivarez@intelliatx.com

Investors:

Lina Li

Associate Director

Investor Relations

+1 857-706-1612

lina.li@intelliatx.com

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Intellia Therapeutics to Present New Preclinical Data from Its CRISPR/Cas9 Programs at the 23rd Annual Meeting of the American Society of Gene and...

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What comic book super heroes and villains tell us about plant and human gene editing and the coronavirus – Genetic Literacy Project

Sunday, April 26th, 2020

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

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

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

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

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

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

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

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

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

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

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

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

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Coronavirus might be changing into less infective form, DU teacher’s research finds – Dhaka Tribune

Sunday, April 26th, 2020

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Did the COVID-19 virus originate from a lab or nature? Examining the evidence for different hypotheses of the novel coronavirus’ origins – Health…

Sunday, April 26th, 2020

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Trevor Bedford

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

Angela Rasmussen

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

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

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

Josh Michaud

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

Ryan McNamara

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

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

Carl T. Bergstrom

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Did this virus come from a lab? Maybe not but it exposes the threat of a biowarfare arms race – Salon

Sunday, April 26th, 2020

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Facts as "rumors"

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

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

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

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

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

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

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

Bioengineered From a lab

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

"Crazy, dangerous"

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

As Boyle saidin 2015:

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

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

Boyle also warned:

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Comment: Nassau executive chef Silvena Rowe on biohacking the body – Caterer Middle East

Sunday, April 26th, 2020

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

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

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

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

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

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

Use supplements strategically

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

Stay active- but rest is just as important

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

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

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

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Researchers Move Closer to Industrial Production of Heparin in Cell Culture – Genetic Engineering & Biotechnology News

Friday, April 17th, 2020

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

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

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

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

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

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

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

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

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

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Better Predicting the Unpredictable Byproducts of Genetic Modification – NC State News

Friday, April 17th, 2020

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

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

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

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

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

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

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

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

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

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

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

-shipman-

Note to Editors: The study abstract follows.

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

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

Published: April 10, PLOS Computational Biology

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

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