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Category Archives: Human Genetic Engineering

CRISPR has brought pig-to-human organ transplants to the cusp of reality – Genetic Literacy Project

In a study published [September 21] in theNature Biomedical Engineeringjournal, the researchers said they usedCRISPRCas9 and a combination of other genetic technologies to inactivate porcine endogenous retroviruses (PERVs), a group of viruses that could be dangerous to humans, while also enhancing the pigs immunological and blood-coagulation compatibility with humans, which could reduce the risk of rejection by organ recipients.

The engineered pigs exhibited normal physiology, fertility and transmission of the edited genes to their offspring, according to the paper.

Transplants from pigs have long been investigated as a solution to the global shortage of human organs for patients with organ failure, for reasons such as the size of their organs similar enough to those of humans and their relatively short maturity period of about six months.

The risks of organ rejection due to the biological incompatibility of pig organs with human bodies and of transmitting PERVs have limited the clinical applicability of such transplants, but advancements in gene-editing technology have given researchers new hope.

George Church, one of the authors from Harvard Medical School and a co-founder of Hangzhou-based Qihan Bio, was quoted by Chinese news agency Xinhua as saying that if the technology used can be further verified in future research, it could help alleviate the global shortage of human organs to a large extent.

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UNH is part of the test-your-sewage-for-COVID team – Granite Geek – Concord Monitor

Testing wastewater for genetic markets indicating COVID-19 is an increasingly popular idea because it can spot outbreaks before they would otherwise be seen. I wrote in August about Keene starting it up UNH has a similar program. Heres their press release:

The University of New Hampshire has gone underground to flush out cases of the coronavirus by testing wastewater on campus. The sewage sampling is being used as a secondary surveillance method to twice a week individual nasal tests to track and detect SARS-CoV-2, the virus that causes COVID-19.

Sewage sampling can be a valuable surveillance tool because it can provide an early warning to possible infection hot spots on campus and help identify areas where the virus may be present but not detected in individuals because they arent showing symptoms, said Paula Mouser, associate professor of civil and environmental engineering.

The wastewater testing, which is being led by a team of environmental engineers in Mousers lab, can identify traces of the viruss genetic material in human sewage. When individuals are infected, the virus is present in their gastrointestinal tract and released in human waste products which move into the sewer lines. Wastewater samples, which contain urine and feces as well as traces of sewage from cooking and laundry, are retrieved from manholes around campus and tested for two biomarkers (N1 and N2) of the SARS-CoV-2 virus. Each manhole accessed represents wastewater from a grouping of two to five dorms known as a mini-sewershed. There are ten residence hall sewersheds currently being tested, representing close to 4400 students, or approximately 80% of those living on campus. Mousers team is also testing wastewater at the local treatment facility to see how the campus signal relates to the biomarker signal in the whole community.

Wastewater testing began when students moved back onto campus for the fall semester. Since the sewer pipes were not in use during part of spring semester and over the summer, wastewater began flowing again when residence halls became occupied. The sensitive test was able to detect a weak baseline level of the viral biomarkers in the wastewater when students returned, which the team believes is related to former infections. The human gastrointestinal tract can shed the virus for several weeks after an individual tests negative with a nasal swab test. Even though students were required to test negative before returning to campus, initial biomarker baseline levels suggest that some students may have been unknowingly infected over the summer. Sewershed biomarker levels have also tracked closely to known infections that occurred in several campus residence halls.

At UNH, wastewater samples are taken three mornings a week. The sample processing is done in the Mouser lab with biomarker quantification conducted with a digital droplet PCR instrument housed at UNHs Hubbard Center for Genome Studies.

If a spike of viral biomarkers is detected in the sewage from one of the dorm groupings, the information is compared with corresponding results from primary nasal swab COVID-19 tests processed at the university testing lab, located at UNH Health & Wellness. Students living on campus are routinely screened every four days with self-swabbing kits. The goal of the wastewater testing program is to correlate any uptick of cases to prevent the spread of the virus and help students get the proper care. According to the World Health Organization, wastewater testing has a long history in virus surveillance and has been used in other outbreaks like the polio virus.

We realized early on the importance of doing virus testing ourselves, said Marc Sedam, vice provost for innovation and new ventures. The wastewater testing has been a useful enhancement for environmental monitoring but not a replacement for our robust campus testing process.

While wastewater testing started as a complimentary monitoring service for the UNH testing lab, Mousers team has heard from a number of schools, wastewater utilities, and healthcare facilities looking for guidance on creating a similar approach and technologies. Her team is working on a pilot program to help organizations apply the biomarker surveillance approach to their own wastewater samples in their communities across the state.

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International Group of Scientists Explain the Advantages of Using Metabolic Engineering to Address Hidden Hunger – Newswise

Newswise ST. LOUIS, MO, October 22, 2020 More than two billion people worldwide suffer from micronutrient malnutrition due to deficiencies in minerals and vitamins. People in developing countries are most affected, as their diets are typically dominated by starchy staple foods, which are inexpensive sources of calories but contain low amounts of micronutrients. In a perspective paper, Multiplying the efficiency and impact of biofortification through metabolic engineering, recently published in Nature Communications, an international team of scientists, led by Ghent University, explain how plant genetic engineering can help to sustainably address micronutrient malnutrition.

Micronutrient malnutrition leads to severe health problems. The highest numbers of people affected by mineral and vitamin deficiencies live in Africa and Asia. For instance, vitamin A and zinc deficiency are leading risk factors for child mortality. Iron and folate deficiency contribute to anemia, physical and cognitive development problems. Often, the people affected are not aware of their nutritional deficiencies, which is why the term hidden hunger is also used. The long-term solutions are that all people are made aware of healthy nutrition through education, and raising incomes so that all can afford a balanced diet all year round. However, more targeted interventions are required in the short and medium run.

One intervention is to breed staple food crops for higher micronutrient contents, also known as biofortification. Over the last 20 years, international agricultural research centers have developed biofortified crops using conventional breeding methods, including sweet potato and maize with vitamin A and wheat and rice with higher zinc contents. These crops were successfully released in various developing countries with proven nutrition and health benefits. However, conventional breeding approaches have certain limitations.

In the Nature Communications perspective, the scientists report how genetic engineering can help to further enhance the benefits of biofortified crops. Transgenic approaches allow us to achieve much higher micronutrient levels in crops than conventional methods alone, thus increasing the nutritional efficacy. We demonstrated this for folates in rice and potato, says Dominique Van Der Straeten from Ghent University in Belgium, the papers lead author. We also managed to reduce post-harvest vitamin losses significantly, she adds.

Another advantage of genetic engineering is that high amounts of several micronutrients can be combined in the same crop. This is very important, as impoverished people often suffer from multiple micronutrient deficiencies, says co-lead Howarth Bouis from the International Food Policy Research Institute and 2016 World Food Prize winner.

Genetic engineering can also help to combine micronutrient traits with productivity-increasing agronomic traits, such as drought tolerance and pest resistance, which are becoming ever more relevant with climate change. Farmers should not have to make difficult choices between crops that either improve nutrition or allow productive and stable harvests. They need both aspects combined, which will also support widespread adoption, says co-author Donald MacKenzie, PhD, executive director of the Institute for International Crop Improvement at the Donald Danforth Plant Science Center.

The authors acknowledge that genetic engineering is seen skeptically by many, even though research shows that the resulting crops are safe for human consumption and the environment. However, the publics reservations around genetic engineering, which may often be conflated with concerns around corporate concentration in agriculture, may be lessened by more support of public sector and humanitarian efforts. One of the reasons for the public reservations is also that genetic engineering is often associated with large multinational companies. Biofortified crops may possibly reduce some of the concerns, as these crops are developed for humanitarian purposes. Public funding is key to broader acceptance, said MacKenzie.

Scientists from the following organizations contributed to the paper (in alphabetical order):

About The Donald Danforth Plant Science CenterFounded in 1998, theDonald Danforth Plant Science Centeris a not-for-profit research institute with a mission to improve the human condition through plant science. Research, education and outreach aim to have impact at the nexus of food security and the environment, and position the St. Louis region as a world center for plant science. The Centers work is funded through competitive grants from many sources, including the National Institutes of Health, U.S. Department of Energy, National Science Foundation, and the Bill & Melinda Gates Foundation. Follow us on Twitter at@DanforthCenter

Media contact: Karla Roeber, (314) 406-4287, kroeber@danforthcenter.org

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Gene-edited crops and animals: Best-kept secrets in the fight against climate change – Genetic Literacy Project

Advances in gene editing over the past decade have given scientists new tools to tailor the biochemistry of nearly any living thing with great precision. Because the biosphereincluding trees, crops, livestock, and every other organismsis a major source and sink for greenhouse gases (GHGs), these tools have profound implications for climate change. Gene editing is unlocking new ways to enhance natural and agricultural carbon sinks, limit emissions from agriculture and other major GHG-emitting sectors, and improve biofuels. Congress should act now to open this new frontier for climate innovation.

Gene editing uses enzymesCRISPR Cas9 is the most well-knownto identify, remove, and replace segments of an organisms DNA, much like using a word processor to edit a document. These tools originated as defense mechanisms so that bacteria could remove foreign DNA inserted by predatory viruses. Researchers have adapted this cellular machinery to introduce beneficial traits into plants and animals. The techniques are new, but they build on nearly a half century of experience with conventional genetic engineering and hundreds of millions of years of evolution.

Zooming out from the microscopic level, gene editing offers novel solutions to a diverse set of emissions-related problems.

The Trillion Trees initiative recognizes plants unique ability: using photosynthesis to capture carbon. Yet the process is surprisingly inefficient.Scientistshave moved swiftly to use their new toolkit to try to improve it, and several breakthroughs have already been reported. Further progress might enableproductivity gainsof 50 percent in major crops, slashing emissions radically, raising output per acre, and bolstering farmers incomes.

The decomposition and transport of wasted food accounts for the single largest portion of agricultural GHG emissions. Companies are already selling gene-editedsoybean oilwith a longer shelf life andpotatoesthat resist bruising, both of which reduce waste.

Next-generation biofuels from switchgrass, which grows easily on otherwise non-arable land, could power sustainable, low-carbon transport. The hitch has been that this plants key ingredient, cellulose, is hard to break down. Gene editing may open up this abundant resource by optimizing microbes that can efficiently process cellulose, yielding low-cost biofuels and spurring rural development.

The worlds 1.4 billion cattle account for about6 percentof global agriculture GHG emissions, in large part because of methane in their burps. Some cattle emit far less methane than others because of specific microbial populations in their digestive tracts. Gene editing could allow this trait to spread across herds,reducing emissions.

Gene editings enormous promise for solving societal problems, including climate change, has been slowed by concerns that it is neither natural nor safe. These concerns are misplaced. Humans have used breeding to shape the genomes of crops and livestock since the dawn of agriculture. Our new gene editing toolkit has been used by nature for hundreds of millions of years. Most important, in eleven major studies over the past four decades, the U.S. National Academy of Sciences hasfoundno new hazards in gene edited or genetically engineered products. Other authoritative bodies around the world have drawn the same conclusion, which has been confirmed by vast experience.

The urgency of the climate challenge is becoming clearer with each passing season as severe storms, droughts, fires, and other disasters become more frequent at home and around the world. Congress should take action today to accelerate gene-edited climate solutions. First, legislators should eliminate regulatory burdens that disincentivize innovation in gene-edited technologies and contribute little to human or environmental safety. Current regulations on gene-edited products have addedtens of millions of dollarsand multiple years to their development without delivering commensurate benefits for health, safety, or the environment.

Second, Congress should create a new agency to support agricultural research into high-reward biological technologies including gene editing. The ARPA-Terra Act of 2019 (S.2732) introduced by Sen. Michael Bennet would do so, emulating the highly successful models of the Defense Advanced Research Projects Agency (DARPA) and the Advanced Research Projects Agency-Energy (ARPA-E).

Finally, Congress should encourage innovative farmers to adopt new gene-edited crops and livestock to demonstrate their value and speed wider deployment. Existing tax credits for carbon capture could be expanded as these nascent products come to market.

Although gene editing is less than a decade old, it is already abundantly clear that it will be a powerful tool to address climate change. The science is ready and waiting for Congressional action.

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Aridis Pharmaceuticals, Inc. to Present at the ROTH Capital Healthcare Event "COVID-19 Therapeutics in Development" – PRNewswire

SAN JOSE, Calif., Oct. 27, 2020 /PRNewswire/ -- Aridis Pharmaceuticals, Inc. (Nasdaq: ARDS), a biopharmaceutical company focused on the discovery and development of novel anti-infective therapies to treat life-threatening infections, today announced the Company will present at theROTH Capital Healthcare Event "COVID-19 Therapeutics in Development"on Wednesday, October 28, 2020. Dr. Hasan Jafri, Chief Medical Officer of Aridis Pharmaceuticals, will be a speaker on a panel entitled "Direct Antivirals and Other Agents Against SARS-CoV2 Virus."

Panel:Direct Antivirals and Other Agents Against SARS-CoV2 VirusDate: Wednesday, October 28, 2020Time:10:30AM-11:50AM ET

Dr. Jafri will present a summary of the Company's recently published preclinical data of its COVID-19 inhaled mAb (AR-711). He will address the preclinical performance of AR-711, the advantages of direct lung delivery using nebulized aerosols, and the COVID-19 clinical program.

About AR-711

AR-711 is a fully human immunoglobulin 1, or IgG1, monoclonal antibody discovered from screening the antibody secreting B-cells of convalescent COVID-19 patients. AR-711 exhibits high affinity for SARS-CoV-2 spike protein, approximately 10-fold or higher than mAb candidates currently in late stage clinical testing. AR-711 was previously shown to be effective in prophylactic as well as therapeutic treatment modes in a SARS-CoV-2 viral challenge study. AR-711 is currently being developed as an inhaled, self-administered treatment for non-hospitalized patients suffering from mild to moderate COVID-19. AR-711 is also one the two mAbs in the company's AR-701 mAb cocktail, which is a separate program being developed as an intravenous treatment of moderate to severe, hospitalized COVID-19 patients.

About Aridis Pharmaceuticals, Inc.

Aridis Pharmaceuticals, Inc. discovers and develops anti-infectives to be used as add-on treatments to standard-of-care antibiotics. The Company is utilizing its proprietary PEXTM and MabIgX technology platforms to rapidly identify rare, potent antibody-producing B-cells from patients who have successfully overcome an infection, and to rapidly manufacture monoclonal antibody (mAbs) for therapeutic treatment of critical infections. These mAbs are already of human origin and functionally optimized for high potency by the donor's immune system; hence, they technically do not require genetic engineering or further optimization to achieve full functionality.

The Company has generated multiple clinical stage mAbs targeting bacteria that cause life-threatening infections such as ventilator associated pneumonia (VAP) and hospital acquired pneumonia (HAP), in addition topreclinical stage antiviral mAbs. The use of mAbs as anti-infective treatments represents an innovative therapeutic approach that harnesses the human immune system to fight infections and is designed to overcome the deficiencies associated with the current standard of care which is broad spectrum antibiotics. Such deficiencies include, but are not limited to, increasing drug resistance, short duration of efficacy, disruption of the normal flora of the human microbiome and lack of differentiation among current treatments. The mAb portfolio is complemented by a non-antibiotic novel mechanism small molecule anti-infective candidate being developed to treat lung infections in cystic fibrosis patients. The Company's pipeline is highlighted below:

Aridis'Pipeline

AR-301(VAP).AR-301 is a fully human IgG1 mAb currently in Phase 3 clinical development targeting gram-positiveStaphylococcus aureus (S. aureus)alpha-toxin in VAPpatients.

AR-101(HAP).AR-101 is a fully human immunoglobulin M, or IgM, mAb in Phase 2 clinical development targetingPseudomonas aeruginosa (P. aeruginosa)liposaccharides serotype O11, which accounts for approximately 22% of allP. aeruginosahospital acquired pneumonia cases worldwide.

AR-501(cystic fibrosis).AR-501 is an inhaled formulation of gallium citrate with broad-spectrum anti-infective activity being developed to treat chronic lung infections in cystic fibrosis patients. This program is currently in a Phase 1/2a clinical study in healthy volunteers and CF patients.

AR-401(blood stream infections).AR-401 is a fully human mAb preclinical program aimed at treating infections caused by gram-negativeAcinetobacter baumannii.

AR-701(COVID-19). AR-701 is a cocktail of fully human mAbs discovered from convalescent COVID-19 patients that are directed at multiple envelope proteins of the SARS-CoV-2 virus.

AR-711(COVID-19). AR-711 is an in-licensed mAb that is directed against the receptor binding domain of the SARS-Cov 2 virus. The agent has the potential to be delivered both intravenously and by inhalation using a nebulizer.

AR-201(RSV infection). AR-201 is a fully human IgG1 mAb out-licensed preclinical program aimed at neutralizing diverse clinical isolates of respiratory syncytial virus (RSV).

For additional information on Aridis Pharmaceuticals, please visithttps://aridispharma.com/.

Forward-Looking Statements

Certain statements in this press release are forward-looking statements that involve a number of risks and uncertainties. These statements may be identified by the use of words such as "anticipate," "believe," "forecast," "estimated" and "intend" or other similar terms or expressions that concern Aridis' expectations, strategy, plans or intentions. These forward-looking statements are based on Aridis' current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, the need for additional financing, the timing of regulatory submissions, Aridis' ability to obtain and maintain regulatory approval of its existing product candidates and any other product candidates it may develop, approvals for clinical trials may be delayed or withheld by regulatory agencies, risks relating to the timing and costs of clinical trials, risks associated with obtaining funding from third parties, management and employee operations and execution risks, loss of key personnel, competition, risks related to market acceptance of products, intellectual property risks, risks related to business interruptions, including the outbreak of COVID-19 coronavirus, which could seriously harm ourfinancial condition and increase our costs and expenses, risks associated with the uncertainty of future financial results, Aridis' ability to attract collaborators and partners and risks associated with Aridis' reliance on third party organizations. While the list of factors presented here is considered representative, no such list should be considered to be a complete statement of all potential risks and uncertainties. Unlisted factors may present significant additional obstacles to the realization of forward-looking statements. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, market conditions and the factors described under the caption "Risk Factors" in Aridis' 10-K for the year ended December 31, 2019 and Aridis' other filings made with the Securities and Exchange Commission.Forward-looking statements included herein are made as of the date hereof, and Aridis does not undertake any obligation to update publicly such statements to reflect subsequent events or circumstances.

Contact:

Investor RelationsJason WongBlueprint Life Science Group[emailprotected](415) 375-3340 Ext. 4

SOURCE Aridis Pharmaceuticals, Inc.

SOURCE Aridis Pharmaceuticals, Inc.

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No evidence that coronavirus genetic sequences were fabricated, contrary to preprint by Li-Meng Yan and colleagues – Health Feedback

CLAIM

Fabricated genetic sequences were used to support the hypothesis that the virus arose naturally

DETAILS

Inadequate support: The preprint by Yan et al. offers no evidence to support their claim that the genetic sequences of other coronavirus strains were fabricated to support the hypothesis that SARS-CoV-2 arose naturally.Incorrect: The fact that multiple coronavirus strains share highly similar or identical genetic or protein sequences is not evidence that those viruses were fabricated. Shared genetic or protein sequences is common among viruses that belong to the same family and indicates their evolutionary relatedness.

KEY TAKE AWAY

There is no evidence supporting the claim by Yan et al. that genetic sequences of several coronaviruses were fabricated to support the hypothesis that SARS-CoV-2 arose naturally. The presence of highly similar or identical gene and protein sequences are common among organisms that are evolutionarily related to each other. Therefore, it is expected that members of the coronavirus family share similar or identical genetic or protein features. Scientific evidence supports the hypothesis that the virus arose naturally in wildlife before it crossed over to humans.

REVIEW Uncertainty surrounding the origin of the novel coronavirus has provided fertile ground for breeding conspiracy theories, some of which Health Feedback previously found to be inaccurate and unsubstantiated (see here and here). The recent claim by virologist Li-Meng Yan that the SARS-CoV-2 virus is manmade is the latest in a long series of conspiracy theories stretching back to the beginning of the coronavirus pandemic.

On 14 September 2020, Yan and her colleagues published a preprint on the online repository Zenodo claiming that the SARS-CoV-2 virus is a product of genetic engineering. A preprint is a research paper that has not been peer-reviewed by other scientists yet. Experts who examined the preprint found it was highly flawed and provided no supporting evidence for their claims, as detailed in this Health Feedback review.

Yan et al. published a second preprint on 8 October 2020 claiming that the virus is an unrestricted bioweapon and alleging that the genetic sequences of ten other coronaviruses are fabricated and do not exist in nature. Contrary to this claim, these ten coronaviruses, including RaTG13which is the closest known relative to SARS-CoV-2 and has about 96% genome sequence identity to SARS-CoV-2[1]and some pangolin coronaviruses, were analyzed by other scientists and found to support the natural origin hypothesis for SARS-CoV-2[2-7]. The second preprint from Yan et al. received more than 130,000 views on Zenodo since it was published, and was promoted by outlets known for publishing misinformation, such as Zero Hedge and National Pulse.

The alleged motivation for fabricating genetic sequences is related to one of the primary claims by Yan et al., specifically that the bat coronaviruses ZC45 and ZXC21 provided the genetic backbone for SARS-CoV-2. In support of this claim, Yan et al. point to the 100% identity in the envelope (E) protein sequence that exists between these three viruses. The E protein is a small protein on the surface of the membrane that encloses the viral genome and is important for producing virus particles that can efficiently infect cells[8].

Firstly, the claim that the bat coronaviruses ZC45 and ZXC21 provided the genetic backbone to artificially create SARS-CoV-2 was presented in the first preprint by Yan et al. This claim was debunked by scientists, who pointed out that the genetic sequences of ZC45 and ZXC21 are very different to that of SARS-CoV-2. In fact, the virus ZC45 is only 89% related to SARS-CoV-2, said Stanley Perlman, a professor at the University of Iowa who studies coronaviruses, in this FactCheck.org article:

Perlman said it would be nearly impossible to make the reverse genetics system needed to manipulate the virus and changing its sequence to arrive at SARS-CoV-2 would be virtually impossible since it would not be known how to manipulate the virus.

Kristian Andersen, a professor at Scripps Research who studies the evolution of viruses including SARS-CoV-2, also pointed out the incongruency of the claim on Twitter: This simply cant be true there are more than 3,500 nucleotide differences between SARS-CoV-2 and these viruses.

Marvin Reitz, a virologist at the University of Maryland, put it more bluntly in his review of the first preprint: [I]t still would require more than 3,000 nucleotide substitutions [for ZC45] to become SARS-CoV-2. This is not even slightly credible; it beggars reason.

A response by scientists at the Johns Hopkins University Center for Health Security also provides a detailed rebuttal of the claims made by Yan et al. in their first preprint. It also highlights the implausible use of ZC45 and ZXC21 as the genetic backbone for SARS-CoV-2.

In short, ZC45 and ZXC21 are very different from SARS-CoV-2 in terms of genome identity. Altering a backbone from either of the two to transform it into the genome of SARS-CoV-2 would require a feat of genetic engineering that is extremely difficult, if not impossible, to accomplish with current technology.

Based on their spurious initial assumption that ZC45 and ZXC21 provided the genetic backbone for SARS-CoV-2, Yan et al. claim that the genetic sequences of RaTG13 and the other coronaviruses were fabricated to obscure the link between SARS-CoV-2 and ZC45/ZXC21, and that RaTG13 and the other coronaviruses do not exist. To support this claim, they point to the observation that all these viruses also have an E protein sequence that is 100% identical to that of ZC45 and ZXC21.

The argument by Yan et al. that the genetic sequences of some coronaviruses were fabricated to support the hypothesis that SARS-CoV-2 arose naturally does not hold up to scrutiny. In a Business Insider interview, Emma Hodcroft, a postdoctoral fellow at the University of Basel and co-developer of the Nextstrain project that studies the evolution of pathogens, including SARS-CoV-2, pointed out that most of the samples that Yans group says are fake predate the start of the pandemic. Hodcroft also explained:

This accusation implies there were years of coordination and fake sequence generation, Hodcroft said, adding: This is an incredible claim, and would require a significant evidence burden to back it up, which is missing from the paper.

Virologists have also analyzed the genome sequence of RaTG13 and found it to be authentic and supported by good-quality data.

Although some coronaviruses share certain identical genetic sequences with SARS-CoV-2, this is not evidence that the other coronaviruses were fabricated. Instead, similar or identical genetic and protein sequences of coronaviruses are evidence of their evolutionary relatedness, which is expected since these viruses all belong to the coronavirus family. Specifically, the E protein sequence of SARS-CoV-2, RaTG13, and the other coronaviruses analyzed in the preprint by Yan et al. are indeed identical to that of ZC45 and ZXC21, but this in itself does not indicate that the RaTG13 and the other coronaviruses were fabricated to mimic the E protein sequence of ZC45 and ZXC21.

Lastly, one feature of concern in both preprints by Yan and her co-authors is the listing of their affiliations as the Rule of Law Society and the Rule of Law Foundation. These two organizations have no prior experience in conducting biological research and are linked to Stephen Bannon and Wengui Guo, both of whom have published COVID-19 misinformation in the past.

Overall, the claims in the second preprint by Yan and her colleagues are as ill-founded as the claims made in their first preprint. Evidence supporting claims that the virus was engineered is lacking. In contrast, scientific analyses support the hypothesis that SARS-CoV-2 arose naturally in wildlife before crossing over to humans during a zoonotic infection (transmission of pathogens from animals/insects to humans). There are numerous examples of emerging zoonotic pathogens causing disease outbreaks throughout human history and across the world[9].

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