Through the social and economic disruption that COVID-19 caused in 2020, the biomedical research community rose to the challenge and accomplished unprecedented feats of scientific acumen. With a new year ahead of us, even as the pandemic grinds on, we at The Scientist thought it was an opportune time to ask what might be on the life science innovation radar for 2021 and beyond. We tapped three members of the independent judging panel that helped name our Top 10 Innovations of 2020 to share their thoughts (via email) on the year ahead.

Paul Blainey: Value is shifting from the impact of individual technologies (mass spectrometry, cloning, sequencing, PCR, induced pluripotent stem cells, next generation sequencing, genome editing, etc.) to impact across technologies. In 2021, I think researchers will increasingly leverage multiple technologies together in order to generate new insights, as well as become more technology-agnostic as multiple technologies present plausible paths toward research goals.

Kim Kamdar: Partially in reaction to the COVID-19 pandemic, one 2021 headline will be the continued innovation focused on consumerization of healthcare, which is redefining how consumers engage with providers across each stage of care. Consumers are even selective about their healthcare choices now, and the retail powerhouses like CVS and Walmart have and will continue to develop solutions to meet the needs of their customers. While this was already underway prior to the pandemic, the crisis has spurred on this activity with the goal of making healthcare more accessible and affordable and ultimately delivering on better health outcomes for all Americans.

Robert Meagher: I think this is easymRNA delivery. This is something that has been in development for years for numerous applications, but the successful development and FDA emergency use authorization of two COVID-19 vaccines based on this technology shines a very bright spotlight on this technology. The vaccine trials and now widespread use of the vaccines will give developers a lot of data about the technology, and sets a baseline for understanding safety and side effects when considering future therapeutic applications outside of infectious disease.

PB:Single-cell technology is here to stay, although its use will continue to change. One analogy to be drawn is the shift we saw from the popularity ofde novo genome sequencing (during the human genome project and the early part of the NGS [next-generation sequencing] era to the rich array of re-sequencing applications practiced today. I expect new ways to use single-cell technology will continue to be discovered for some time to come.

KK: Innovation in single-cell technology has the potential to transform biological research driving to a level of resolution that provides a more nuanced picture of complex biology. Cost has been a key barrier for broader adoption of single-cell analysis. As better technology is developed, cost will be reduced and there will be an explosion in single-cell research. This dynamic will also allow for broader adoption of single-cell technology from translational research to clinical applications particularly in oncology and immunology.

RM: Yesthere is continuing innovation in this space, and room for continued innovation. One area that we have seen development recently, and I see it continuing, is to study single cells not just in isolation, but coupled with spatial information: understanding single cells and their interactions with their neighbors. I also wonder if the COVID-19 pandemic will spur increased interest in applying single-cell techniques to problems in infectious disease, immunology, and microbiology. A lot of the existing methods for single-cell RNA analysis (for example) work well for human or mammalian cells, but dont work for bacteria or viruses.

PB: The promises of CRISPR and gene editing are extraordinary. I cant wait to see how that field continues to develop.

KK: Much of the CRISPR technology focus since it was unveiled in 2012 has been on its utility to modify genes in human cells with the goal of treating genetic disease. More recently, scientists have shown the potential of using the CRISPR gene-editing technology for treatment of viral disease (essentially a programmable anti-viral that could be used to treat diseases like HIV, HBV, SARS, etc. . . .). These findings, published in Nature Communications, showed that CRISPR can be used to eliminate simian immunodeficiency virus (SIV) in rhesus macaque monkeys. If replicated in humans, in studies that will be initiated this year, CRISPR could be utilized to address HIV/AIDS and potentially make a major impact by moving a chronic disease to one with a functional cure.

PB: New therapeutic modalities that expand the addressable set of diseases are particularly exciting. Cell-based therapies offer versatile platforms for biological engineering that leverage the power of human biology. It is also encouraging to see somatic cell genome editing technology advance toward the clinic for the treatment of serious diseases.

The level of innovation that occurred in 2020 to combat COVID-19 will provide a more rapid, focused, and actionable reaction to future pandemics.

Kim Kamdar, Domain Associates

RM: Besides the great success with mRNA-based vaccines that sets the stage for other clinical technologies based on mRNA delivery, the other area that is really in the spotlight this year is diagnostics. There are a lot of labs and companies, both small and large, that have some really innovative products and ideas for portable and point-of-care diagnostics. For a long time, this was often thought of in terms of a problem for the developing world, or resource-limited locations: think, for example, of diagnostics for neglected tropical diseases. But the COVID-19 pandemic and the associated need for diagnostic testing on a massive scale has caused us to rethink what resource-limited means, and to understand the challenge posed by bottlenecks in supply chains, skilled personnel, and high-complexity laboratory facility. There has been a lot of foundational research over the past couple of decades in rapid, portable, easy-to-use diagnostics, but translating these to clinically useful products often seemed to stall, I suspect for lack of a lucrative market for such tests. But we are now starting to see FDA [emergency use authorization for] home-based tests and other novel diagnostic technologies to address needs with the COVID-19 pandemic, and I suspect that this paves the way for these technologies to start being applied to other diagnostic testing needs.

PB: Seeing the suffering and destruction wrought by COVID-19, it is obvious that we need to be prepared with more extensive, equitable, and better-coordinated response plans going forward. While rapid vaccine development and testing were two bright spots last year, there are so many important areas that demand progress. As we learn about how important details become in a crisisno matter how small or mundanediagnostic technologies and the calibration of public health measures are two areas that merit major focus.

KK: The life science community response to the COVID-19 pandemic has already proven to be light-years ahead of previous responses particularly in areas such as vaccine development and diagnostics. It took more than a year to sequence the genome of the SARS virus in 2002. The COVID-19 genome was sequenced in under a month from the first case being identified. Scientists and clinicians were able to turn that initial information to multiple approved vaccines at a blazing speed. Utilizing messenger RNA (mRNA) as a new therapeutic modality for vaccine development has now been validated. Vaccine science has been forever changed. The pandemic has also focused a much-needed level of attention to diagnostics, forcing a rethink of how to increase access, affordability, and actionability of diagnostic testing. The level of innovation that occurred in 2020 to combat COVID-19 will provide a more rapid, fo
cused, and actionable reaction to future pandemics. In addition, the elevation of a science advisor (Dr. Eric Lander) to a cabinet level position in the Biden administration bodes well for our future ability to ground in data and as President Biden himself framed, refresh and reinvigorate our national science and technology strategy to set us on a strong course for the next 75 years, so that our children and grandchildren may inhabit a healthier, safer, more just, peaceful, and prosperous world.

RM: One thing that really kick-started research to address COVID-19 was the early availability of the complete genome sequence of the SARS-CoV-2 virus, and the ongoing timely deposition of new sequences in nearreal-time as isolates were sequenced. This is in contrast to cases where deposition of large number of sequences may lag an outbreak by months or even years. I foresee the nearreal-time sharing of sequence information to become the new standard. Making the virus itself widely and inexpensively available, in inactivated form, as well as well-characterized synthetic viral RNA standards and proteins also helped spur research.

A trend Im less fond of is the rapid publication of nonpeer reviewed results as preprints online. Theres a great benefit to getting new information out to the community ASAP, but unfortunately I think the rush to get preprints up in some cases results in spreading misleading information. This problem is compounded with uncritical, breathless press releases accompanying the posting of preprints, as opposed to waiting for peer-review acceptance of a manuscript to issue a press release. I think the solution may lie in journals considering innovative approaches to speeding up peer review, or a way to at least perform a basic check for rigor prior to posting a preliminary version of the manuscript. Right now the extremes are: post an unreviewed preprint, or wait months or even years with multiple rounds of peer review including extensive additional experiments to satisfy the curiosity of multiple reviewers for high impact publications. Is there a way to prevent manuscripts from being published as preprints with obvious methodological errors or errors in statistical analysis, while also enabling interesting, well-done yet not fully polished manuscripts to be available to the community?

Paul Blaineyis an associate professor of biological engineering at MIT and a core member of the Broad Institute of MIT and Harvard University. The Blainey lab integrates new microfluidic, optical, molecular, and computational tools for application in biology and medicine. The group emphasizes quantitative single-cell and single-molecule approaches, aiming to enable studies that generate data with the power to reveal the workings of natural and engineered biological systems across a range of scales. Blainey has a financial interest in several companies that develop and/or apply life science technologies: 10X Genomics, GALT, Celsius Therapeutics, Next Generation Diagnostics, Cache DNA, and Concerto Biosciences.

Kim Kamdaris managing partner at Domain Associates, a healthcare-focused venture fund creating and investing in biopharma, device, and diagnostic companies. She began her career as a scientist and pursued drug-discovery research at Novartis/Syngenta for nine years.

Robert Meagheris a principal member of Technical Staff at Sandia National Laboratories. His main research interest is the development of novel techniques and devices for nucleic acid analysis, particularly applied to problems in infectious disease, biodefense, and microbial communities. Most recently this has led to approaches for simplified molecular diagnostics for emerging viral pathogens that are suitable for use at the point of need or in the developing world. Meaghers comments represent his professional opinion but do not necessarily represent the views of the US Department of Energy or the United States government.

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Experts Predict the Hottest Life Science Tech in 2021 and Beyond - The Scientist

Some bacteria are abundant in specific locations while absent from others. But, how did the bacteria get into the wrong place? How do we add the good bacteria into the right place when the biogeography has gotten out of whack?

Bacterias are so tiny and small that it is difficult to characterize which subgroups of bacteria live and what genes or metabolic abilities allow them to thrive in these wrong places.

Scientists from Harvard University studied the human oral microbiome and discovered impressive variability in bacterial subpopulations living in some mouth regions.

Co-author A. Murat Eren, assistant professor in the Department of Medicine at the University of Chicago, said, The mouth is the perfect place to study microbial communities. Not only is it the beginning of the GI tract, but its also a very unique and small environment thats microbially diverse enough that we can start to answer interesting questions about microbiomes and their evolution.

The mouth contains a surprising amount of site-specific microbes in different areas. For instance, the microbes found on the tongue are very different from the microbes found on the teeth plaque. Your tongue microbes are more similar to those living on someone elses tongue than they are to those living in your throat or on your gums!

Scientists scoured through public databases and downloaded 100 genomes that represented four bacteria species commonly found in the mouth, Haemophilus parainfluenzae, and the three oral species of the genus Rothia. Using these bacterias as references, scientists tend to discover their relatives sampled in hundreds of volunteers mouths from the Human Microbiome Project (HMP).

Lead author Daniel R. Utter said,We used these genomes as a starting point, but quickly moved beyond them to probe the total genetic variation among the trillions of bacterial cells living in our mouths. Because thats what were curious about, not the arbitrary few that have been sequenced.

Using the approach called metagenomics, scientists deeply examined the genomes of the microbes, which led to a shocking discovery. They found a tremendous amount of variability. What was more surprising was the patterning of that variability across the different parts of the mouth, specifically, between the tongue, cheek, and tooth surfaces.

For example, within a single microbe species, the researchers found distinct genetic forms strongly associated with a single, different site within the mouth. In many cases, the team was able to identify a handful of genes that might explain a particular bacterial groups specific habitat. Applying metagenomics, the scientists were also able to identify specific ways free-living bacteria in peoples mouths differed from their lab-grown relatives.

Colleen Cavanaugh from the Department of Organismic and Evolutionary Biology, Harvard University, said,Having identified some strong bacterial candidates that could determine adaptation to a particular habitat, we would like to test these hypotheses experimentally. These findings could potentially be the key to unlocking targeted probiotics, where scientists could use whats been learned about each microbes habitats requirements to engineering beneficial microbes to land in a specified habitat.

Co-author Jessica Mark Welch, an associate scientist at the Marine Biological Laboratory, said,The mouth is so easily accessible that people have been working on bacteria from the mouth for a long time.

Every environment we look at has these complicated, complex communities of bacteria, but why is that? Understanding why these communities are so complex and how the different bacteria interact will help us better understand how to fix a bacterial community thats damaging our health, telling us which microbes need to be removed or added back in.

Utter said,This study and others like it can provide new insights on the role of oral microbes in human health. The ability to identify specific genes behind habitat adaptation has been somewhat of a holy grail in microbial ecology. We are very excited about our contributions in this area!

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A closer look at the genomes of microbial communities in the human mouth - Tech Explorist

Genetically modified crops could provide a solution to the world hunger problem, but how serious are the risks for our ecosystems?pixnio.com

Just over 20 years ago, agroup of environmental activistsdestroyed experimental GM maize being grown on a Norfolk farm in a landmark act of protest, which brought genetically-engineered crops into the public eye, and was followed by global demonstrations and the adoption of severely restrictive legislature by the EU. Whilst some of the major food-producing countries of the world have become more open to genetically-engineered crops, public attitudes still remain largely hostile. In the UK, 40% of adults surveyed in 2012 believed the government should not be endorsing the use of genetically-engineered crops. These expressions of distrust largely stem from a lack of understanding surrounding genetically-engineered crops asurvey in 2019 found that only 32% of UK adults felt informed about GM crops, and misinformation spread by anti-GMO campaigns has done nothing to alleviate this.

In reality, the facts of genetic engineering are far simpler than such campaigns would make them appear.

In reality, the facts of genetic engineering are far simpler than such campaigns would make them appear. Earlier efforts mainly relied on the use of the bacterium Agrobacterium tumefaciens to introduce foreign DNA into the genome of a plant embryo, and the use of antibiotic-resistance marker genes to select transformed plants. This initially gave rise to fears of spreading antibiotic resistance through genetic engineering, although these marker genes have generally been replaced by plant-derived markers in the transformation process.

With the advent of CRISPR-Cas9 technology, however, engineering of plant genomes has become significantly easier. CRISPR-Cas9 utilises a mechanism found in prokaryotic immune systems, in which characteristic DNA sequences of potentially harmful bacteria are stored in a cluster of sequences, known as CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). These sequences can be transcribed and used to guide the DNA-cleaving activity of the Cas9 protein in genetic engineering, guide RNA for a locus in the plant genome is used to target cuts. CRISPR-Cas9 technology is proving crucial in genetic engineering, thanks to the ease with which endogenous genes can be edited without inserting foreign DNA, which helps the public image of genetically-engineered crops.

But whilst health risks of genetically-engineered crops on the market have been rigorously examined and disproved, these crops are not without their faults. One of the greatest risks posed by transgenic crops is the potential for transgene flow into wild crop relatives, potentially conferring pest or herbicide resistance. Whilst experimental crops are isolated to reduce this risk, this is often not possible for commercial crops, and evidence suggests some small-scale spread of transgenic traits occurring around fields of transgenic crops. The difficulty in preventing transgene spread, however, is that the methods used for instance, pollen sterility can prevent farmers from harvesting and replanting seeds, forcing them to repeatedly buy expensive seed from the developers. This may create a financial barrier to the benefits of such crops for those who might need them most.

Yet with the world population set to hit 8.1 billion by 2025, global solutions are now required to meet the challenges of feeding the growing population in an increasingly adverse climate. Given that roughly 37% of habitable land area is already used in agriculture, the capacity for further expansion is limited, and so increasing the efficacy of crop growth is therefore needed to meet demand. This will likely require the rapid improvement of crops through genetic engineering, with advances in adapting existing plant responses to abiotic stress for instance, increasing the production of osmoprotectants that protect protein structure in drought conditions likely to prove crucial in improving crop productivity whilst minimising strain on land and water resources.

Despite the risks, the improving reliability of transgeniccrop isolation and the benefits of genetically-engineered crops make a compelling case for extending their use. This is especially true for countries experiencing massive population growth, which often also bear the brunt of climate change so what is hindering this?

You dont have to look any further than the case of Golden Rice for the answers. The poster child of the genetically-engineered crop movement, Golden Rice was initially developed in the early 2000s as a transgenic rice strain with aVitamin A content sufficient to provide 80-100% of the RDI in a single cup of rice. This was a solution developed to combat the lack of the vitamin in the diets of many developing countries, with a third of children worldwide estimated to be Vitamin A deficient, leaving them at high risk of death or blindness. Given repeated testing proving both the efficacy and the safety of the rice, it would seem a foregone conclusion that its use in filling the coverage gaps in vitamin supplement distribution would be widely approved. Yet to this day, not a single crop of Golden Rice has been grown outside of experimental trials.

The reasons for this can be traced back to the legislation governing genetically-engineered crops, such as the Cartagena Protocol, which prevents the introduction of new biotechnology should it pose a risk to human or environmental health. Despite very low rates of gene flow from cultivated rice to wild species, and limited evidence to suggest the transgene would persist in wild populations, this protocol was used to ban the introduction of Golden Rice in the EU, which, in conjunction with Greenpeace campaigns, fed fears surrounding the unsafe nature of the crop. However, rulings in recent years appear to be turning the tide; earlier approval from the health authorities of the US, Australia, New Zealand and Canada has been followed by approval in the Philippines and impending approval in Bangladesh, which hopefully signals the start of Golden Rice growth in countries affected by Vitamin A deficiency.

The challenge for the future lies mainly in the general publics understanding and perception of genetic engineering

Although progress is being made in the introduction of genetically-engineered crops, the future of research and development in crop engineering is looking dim. With recent reclassification of GM crops by the EU to include gene-edited crops, those edited using CRISPR-Cas9 are now as severely restricted as transgenic crops. This comes at a time when effective solutions for food production are needed more than ever, and so immediate action is needed if genetically-engineered crop development is to continue. The challenge for the future lies mainly in the general publics understanding and perception of genetic engineering; if improved, this could have considerable influence in producing a more considered approach to GM crop legislation cutting the red tape and allowing the benefits of genetically-engineered crops to reach those most in need.

Varsity is the independent newspaper for the University of Cambridge, established in its current form in 1947. In order to maintain our editorial independence, our print newspaper and news website receives no funding from the University of Cambridge or its constituent Colleges.

We are therefore almost entirely reliant on advertising for funding, and during this unprecedented global crisis, we expect to have a tough few months and years ahead.

In spite of this situation, we are going to look at inventive ways to look at serving our readership with digital content and of course in print too.

Therefore we are asking our readers, if they wish, to make a donation from as little as 1, to help with our running costs at least until this global crisis ends and things begin to return to normal.

Many thanks, all of us here at Varsity would like to wish you, your friends, families an
d all of your loved ones a safe and healthy few months ahead.

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Modified crops modified perspective - Varsity Online

CAMBRIDGE, Mass., Jan. 29, 2021 /PRNewswire/ --Exacis Biotherapeutics, Inc., a development-stageimmuno-oncology company working to harness the immune system to cure cancer,today announcedthe addition of Dirk Huebner,MD,as its Chief Medical Officer. Exacis launched in 2020 to develop next generation mRNA-based cellular therapeutics to treat liquid and solid tumors.

Exacis CEO Gregory Fiore MD said, "Dirk is a wonderful addition and a great fit for our management team. His extensive experience in oncology drug development, including antibody related therapies will be instrumental as we build our pipeline to include high performance stealth edited NK and T cells, with and without CARs (ExaNK, ExaCAR-NK and ExaCAR-T). We look forward to Dirk's insights and medical leadership as we build the company and advance our portfolio."

Dr. Huebner joins Exacis from Mersana Therapeutics where he wasthe Chief Medical Officer,oversaw their clinical developmentand helped build thecompany'sclinical infrastructure. Dr Huebnerhas worked in oncology and immuno-oncology drug development and academiafor more than 25 yearsand brings a deep understanding of the needs in the oncology space as well as the ability to successfully deliverproducts to meet those needs.

Commenting on the new role, Dr. Huebner said, "I am thrilled to join the Exacis team and work with best-in-class technology to create innovative, next-generation engineered NK and T cell therapies that have the potential to improve outcomes and treatment experiences for patients with challenging hematologic and solid tumor malignancies."

About Exacis Biotherapeutics

Exacis is a development stageimmuno-oncologycompany focused on harnessing the human immune system to cure cancer. Exacis uses its proprietary mRNA-based technologies to engineer next generation off-the-shelf NK and T cell therapies aimed at liquid and solid tumors.Exacis was founded in 2020 with an exclusive license to a broad suite of patents covering the use ofmRNA-based cell reprogramming and gene editing technologiesfor oncology.

ExaNK, ExaCAR-NK and ExaCAR-T utilize mRNA cell reprogramming and mRNA gene editing technologies developed and owned by Factor Bioscience. Exacis has an exclusive license to the Factor Bioscience technology for engineered NK and T cell products derived from iPSCs for use in oncology and holds all global development and commercial rights for these investigational candidates.

About T and Natural Killer (NK) Cell Therapies

T and NK cells are types of human immune cells that are ableto recognize and destroy cancer cells and can be modified through genetic engineering to target specific tumors.

SOURCE Exacis Biotherapeutics, Inc.

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Exacis Biotherapeutics Announces Key Addition To Its Executive Leadership Team With Dirk Huebner MD Joining As Chief Medical Officer - PRNewswire

However, in both medicine and dentistry, there is an important role as well for ingenious, low-tech, less expensive approaches to improved health and increased longevity.

The FDA last year approved a high-tech gene therapy drug, Zolgensma, for a rare childhood genetic disease, spinal muscular atrophy, that costs justover $2 millionfor the single dose of the treatment.The illness, which is caused by a defect in a gene calledSMN1, affects about 400 babies in the United States annually and kills those with the most common form of the disease in the first few years of life.The new treatment uses non-pathogenic, genetically engineered viruses to deliver healthy copies of theSMN1gene to patients cells so they can synthesize a protein needed to develop normal muscle neurons.

Another remarkable genetic engineering feat wasreportedin the journalNaturein 2017.An experimental gene therapy procedureused to transform and grow sheets of healthy skin saved the life of a 7-year-old boywho suffered from a genetic disease,junctional epidermolysis bullosa, that had blistered and destroyed most of his skin.He was on the verge of death, but two years after the treatment with genetically engineered cells produced by a multi-national team, he had healthy skin and was leading a normal life.

Those high-tech interventions are spectacular, but there are many simpler and cheaper yet tremendously important innovations for the diagnosis and prevention of illness.Among the most cost-effective are checklists for personnel in operating rooms and ICUs. According to a Norwegian research group, Safety checklists appear to be effective tools for improving patient safety in various clinical settings by strengthening compliance with guidelines, improving human factors, reducing the incidence of adverse events, and decreasing mortality and morbidity.

Sometimes, a simple tool or device is important to clinical diagnosis. One example is the hand-held direct ophthalmoscope, which allows a medical practitioner to look intotheback oftheeye to ascertain the health oftheretina, optic nerve, vasculature, and vitreous humor (the liquid inside the eyeball). Invented in 1851, it costs less than $200.

Another example is the way a singleblood testcan ascertain that a patient in the emergency room is not having a heart attack and so can forego the inconvenience and expense of additional invasive tests or unnecessary hospitalization.The highly sensitive blood test measures levels of cardiac troponin, a protein involved in muscle contraction; if the level is undetectable that is, below the limit of detection of the test there is a greater than 99% likelihood that the patient isnotexperiencing a heart attack and is at very low risk of other cardiac adverse events for at least 30 days.

That innovative approach is advantageous to patients and helps to reduce the frequency of hospitalizations and, therefore, healthcare costs.

Falls are both a cause and effect of declining health in the elderly.They are the leading cause of injury-related visits to emergency rooms and the primary cause of accidental deaths in Americans over the age of 65.To measure the potential benefits of a low-tech approach to preventing injuries from them, a research group in New Zealandcompared rates of falling and injuriesfrom falls on low-impact flooring (LIF) compared with standard vinyl flooring on an older persons health ward.Falls were prospectively monitored with written reports of all incidents, noting the location and consequences of each fall.The frequency of falls and injuries on LIF and those occurring on standard vinyl flooring (controls) were compared.

The investigators found that over the 31months of the study, there were 278 falls (among 178 persons who fell).The rate of falls was indistinguishable in the two groups, but fall-related injuries were significantly less frequent when they occurred on LIFs (22% of falls versus 34% of falls on control flooring).And many of the injuries that were averted were serious: Fractures occurred in 0.7% of falls in the LIF cohort versus 2.3% in the control cohort.

Thus, the New Zealand study provides a compelling rationale for adding low-impact flooring to housing for seniors (along withother modifications).

Dentistry has also benefited from costly high-tech innovations such asdental implants, but low-tech prophylaxis can also provide much needed benefits for dental health.

Tooth decay remains one of the majorpublic health concerns for both developing and developed countriesaccording to the World Health Organization.It is one of the most commonchronic problemsin the United States, where most adults will have at least one cavity in their lifetime. Decay causes inflammation in surrounding gum tissue, abscesses, and eventually, tooth loss. In addition to taking a significant toll on quality of life, decay and periodontitis has been linked to an increased risk of cardiovascular events, systemic infections such as endocarditis, and complications in pregnancy.

There have been significant advances in replacing and restoring teeth that need treatment due to dental caries, and these are often costly. However, preventing the problem in the first place is optimal, and an important advance was the introduction of water fluoridation, a simple low-tech intervention withproven efficacy, in 1945. The concept is that fluoride, a negatively charged ion, binds to calcium and phosphate on tooth surfaces to prevent the bacteria that cause cavities from even entering the tooth, thus protecting the teeth from dental decay and in some cases even reversing early decay. In a systematic review published in 2016, researchersfoundthat fluoridating drinking water in communities decreased overall decay and, thereby, the cost of more aggressive and costly dental interventions.

The Centers for Disease Control estimates that there are approximately100 million Americanswho are still without access to fluoridated water. Introducing this low-tech, high-impact measure more widely would substantially decrease the need for many dental procedures.

The high-tech miracles will continue to garner headlines, but to advance public health, simpler and relatively inexpensive innovations are also essential. That has policy implications: We need to put research dollars not only into potential big-ticket, high-tech blockbusters but also into ingenious, low-tech innovation.

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High-tech medical and dental innovation garner the headlines but the most impactful practices are mostly lower tech and prevention-focused - Genetic...

Its no secret that the United States government has played a huge role in the creation of major technological and medical breakthroughs over the past few hundred years, but did you know that its responsible for many of the devices and products that many people use every day?

If youve ever used a GPS system, you have the Defense Departments research to thank. What about your smartphone? Although the government didnt directly fund the exact phone you own, NASA, the National Science Foundation (NSF), and the CIA were integral in creating crucial elements of todays smartphonessuch as microchips and touch screens. Even the internet, which makes reading this story possible, began as the Advanced Research Projects Agency Network (ARPANET), a computer network first made by the U.S. Defense Advanced Research Projects Agency (DARPA).

Perhaps one of the most consequential fieldsthat hasbenefited most crucially from government support is that of medicine. Many vaccines that prevent millions of Americans from contracting preventable diseasesfrom the common flu to Haemophilus influenzae type Bwere funded and developed with support from the National Institutes of Health (NIH). More recently, the federal initiative Operation Warp Speed was established to facilitate the manufacture and distribution of the coronavirus vaccines.

However, government research and funding have been integral to so many inventions, big and small, that it can be hard to find a starting point when learning about which ones can be credited to various supporting agencies. Stacker compiled information about government-funded creations using a combination of news, scientific, and government reports. The inventions on this list encompass a wide variety of areas, including technology, agriculture, medicine, aviation, and others.

From the beginnings of the civilian aviation industry in 1925 to a recent COVID-19 vaccine breakthrough in 2020, read on to learn about 50 inventions you might not know were funded by the U.S. government.

You may also like: 25 IPOs that bombed on their first day

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50 inventions you might not know were funded by the US government - WFMZ Allentown

SARS-CoV-2, the virus that causes Covid-19, has made our future vulnerability to biological pathogens and what we can learn to help prevent the next pandemic a salient concern. We dont have much evidence one way or the other whether Covids emergence into the world was the result of a lab accident or a natural jump from animal to human. And while the US intelligence communitys current best guess is that the virus probably was not genetically engineered, the theory has been the subject of much debate and has not been definitively ruled out.

The many unknowns we confront underscore the need for a much bigger toolkit to deal with pathogenic threats than we currently have which is why a recent paper about a new advance in tracing genetic editing is particularly exciting.

Bioengineering often leaves traces characteristic patterns in the RNA or DNA of an engineered organism that are a product of a plethora of design decisions that go into synthetic biology. That fact about bioengineered genomes raises an interesting question: What if those traces that gene editing leaves behind were more like fingerprints? That is, what if its possible not just to tell if something was engineered but precisely where it was engineered?

Thats the idea behind genetic engineering attribution: the effort to develop tools that let us look at a genetically engineered sequence and determine which lab developed it. A big international contest among researchers earlier this year demonstrates that the technology is within our reach though itll take lots of refining to move from impressive contest results to tools we can reliably use for bio detective work.

The contest, the Genetic Engineering Attribution Challenge, was sponsored by some of the leading bioresearch labs in the world. The idea was to challenge teams to develop techniques in genetic engineering attribution. The most successful entrants in the competition could predict, using machine-learning algorithms, which lab produced a certain genetic sequence with more than 80 percent accuracy, according to a new preprint summing up the results of the contest.

This may seem technical, but it could actually be fairly consequential in the effort to make the world safe from a type of threat we should all be more attuned to post-pandemic: bioengineered weapons and leaks of bioengineered viruses.

One of the challenges of preventing bioweapon research and deployment is that perpetrators can remain hidden its difficult to find the source of a killer virus and hold them accountable.

But if its widely known that bioweapons can immediately and verifiably be traced right back to a bad actor, that could be a valuable deterrent.

Its also extremely important for biosafety more broadly. If an engineered virus is accidentally leaked, tools like these would allow us to identify where they leaked from and know what labs are doing genetic engineering work with inadequate safety procedures.

Hundreds of design choices go into genetic engineering: what genes you use, what enzymes you use to connect them together, what software you use to make those decisions for you, computational immunologist Will Bradshaw, a co-author on the paper, told me.

The enzymes that people use to cut up the DNA cut in different patterns and have different error profiles, Bradshaw says. You can do that in the same way that you can recognize handwriting.

Because different researchers with different training and different equipment have their own distinctive tells, its possible to look at a genetically engineered organism and guess who made it at least if youre using machine-learning algorithms.

The algorithms that are trained to do this work are fed data on more than 60,000 genetic sequences different labs produced. The idea is that, when fed an unfamiliar sequence, the algorithms are able to predict which of the labs theyve encountered (if any) likely produced it.

A year ago, researchers at altLabs, the Johns Hopkins Center for Health Security, and other top bioresearch programs collaborated on the challenge, organizing a competition to find the best approaches to this biological forensics problem. The contest attracted intense interest from academics, industry professionals, and citizen scientists one member of a winning team was a kindergarten teacher. Nearly 300 teams from all over the world submitted at least one machine-learning system for identifying the lab of origin of different sequences.

In that preprint paper (which is still undergoing peer review), the challenges organizers summarize the results: The competitors collectively took a big step forward on this problem. Winning teams achieved dramatically better results than any previous attempt at genetic engineering attribution, with the top-scoring team and all-winners ensemble both beating the previous state-of-the-art by over 10 percentage points, the paper notes.

The big picture is that researchers, aided by machine-learning systems, are getting really good at finding the lab that built a given plasmid, or a specific DNA strand used in gene manipulation.

The top-performing teams had 95 percent accuracy at naming a plasmids creator by one metric called top 10 accuracy meaning if the algorithm identifies 10 candidate labs, the true lab is one of them. They had 82 percent top 1 accuracy that is, 82 percent of the time, the lab they identified as the likely designer of that bioengineered plasmid was, in fact, the lab that designed it.

Top 1 accuracy is showy, but for biological detective work, top 10 accuracy is nearly as good: If you can narrow down the search for culprits to a small number of labs, you can then use other approaches to identify the exact lab.

Theres still a lot of work to do. The competition looked at only simple engineered plasmids; ideally, wed have approaches that work for fully engineered viruses and bacteria. And the competition didnt look at adversarial examples, where researchers deliberately try to conceal the fingerprints of their lab on their work.

Knowing which lab produced a bioweapon can protect us in three ways, biosecurity researchers argued in Nature Communications last year.

First, knowledge of who was responsible can inform response efforts by shedding light on motives and capabilities, and so mitigate the events consequences. That is, figuring out who built something will also give us clues about the goals they might have had and the risk we might be facing.

Second, obviously, it allows the world to sanction and stop any lab or government that is producing bioweapons in violation of international law.

And third, the article argues, hopefully, if these capabilities are widely known, they make the use of bioweapons much less appealing in the first place.

But the techniques have more mundane uses as well.

Bradshaw told me he envisions applications of the technology could be used to find accidental lab leaks, identify plagiarism in academic papers, and protect biological intellectual property and those applications will validate and extend the tools for the really critical uses.

The past year and a half should have us all thinking about how devastating pandemic disease can be and about whether the precautions being taken by research labs and governments are really adequate to prevent the next pandemic.

The answer, to my mind, is that were not doing enough, but more sophisticated biological forensics could certainly help. Genetic engineering attribution is still a new field. With more effort, itll likely be possible to one day make attribution possible on a much larger scale and to do it for viruses and bacteria. That could make for a much safer future.

Correction, October 25, 9:50 am: A previous version of this story stated that SARS-CoV-2 had been definitively proven not to be a bioengineered virus. While an August 2021 US intelligence report concluded, Most agencies assess with low confidence that SARS-CoV-2 probably was not genetically engineer
ed, and many scientists agree with that assessment, it was an overstatement to claim that the theory has been definitively ruled out. The introduction and conclusion of the story have been updated to reflect this lower level of certainty. (h/t to Alina Chan, biologist at the Broad Institute of MIT and Harvard, for her critique and input)

More here:
How biological detective work can reveal who engineered a virus - Vox.com

The existence of human life on this planet relies entirely on a biochemical process called photosynthesis, which enables green plants to convert sunlight, water, and carbon dioxide into chemical energy in the form of carbohydrates and plant proteins, which humans and and other animals consume in order to sustain their lives. Even among peoples who rely almost entirely on animal foods in their diets due to the extreme climates they live in, such as the Inuit (Eskimo) tribes in Alaska, who live on seal, walrus, and whale meat, survive because those mammals consume small fish, which in turn feed on plankton, algae, and other fish and their eggs. Without plants, there would be no life on this planet.

As I described in a blog in March of 2019, humans are believed to have raised the first domesticated plant species called emmer, an ancestor of modern wheat and barley varieties, about 10,000 years ago in the Middle East. Squash was the first crop domesticated in the Western hemisphere, in ancient Mexico, during the same period. Maize (corn) followed about 2,000 years later, also in meso-America, and rice was first cultivated in the Indus valley in Asia about 4,500 years ago. The youngest of the major food crops which dominate consumption and trade worldwide is soybeans, which was first cultivated in north China more than 3,000 years ago. Combined, corn, wheat, and rice account for about 60 percent of all calories and protein obtained by humans from plants.

When humans migrated across the globe in search of new places to live, they took their staple crops with them, but some of them also found and eventually adopted other crops being raised by the native populations, some of which over time became staple crops to them. As I described in my recently published book on the history of U.S. agricultural policy (co-authored with Dr. Steve Halbrook), many of the new arrivals from Great Britain who had farmed previously, especially those settling in the colonies in the middle Atlantic area such as Pennsylvania and Maryland, insisted on cultivating food crops they were familiar with, such as wheat, rye, and barley. In the northern colonies such as Massachusetts, where most of the new arrivals had not farmed previously, they adopted the crops their native neighbors had farmed for millennia--beans, squash, pumpkins, and maize (corn), using those crops in 3-5 year rotations. In the southern colonies, two of the most important crops were not produced for food--tobacco and cotton, both of which were first grown in the Jamestown settlement in Virginia in the 1610s with seeds brought from Caribbean islands.

While throughout history, farmers have sought to identify and preserve good performing seeds for their crops, the first scientifically based crop breeding work did not occur until after the groundbreaking work of Gregor Mendel in the middle of the 19th century. Mendel was an Austrian monk who demonstrated the rules of heredity by systematically cross-breeding pea plants and studying the traits which appeared in the offspring plants. However, the full significance of Mendel's work was not recognized until nearly the turn of the 20th century (more than three decades later) with the rediscovery and application of his laws to commercial plant breeding efforts. John Garton, an English agriculturalist, was one of the first to cross-pollinate agricultural plants and commercialize the newly created varieties. He began experimenting with the artificial cross pollination initially of cereal plants in the 1890s, then branched out to herbage species and root crops and developed far reaching techniques in plant breeding

The next major breakthrough came with the shuttle breeding approach developed by Dr. Norman Borlaug in his work on wheat at the institute that eventually became CIMMYT (International Wheat and Maize Research) outside of Mexico City, starting in the late 1940s. Working in a mild climate that allowed for multiple crops in a year in different growing conditions, he was able to relatively quickly identify and refine traits that led to high-yielding, disease resistant varieties of wheat that were eventually adopted in many parts of the world. This work earned him the Nobel Peace Prize in 1970, for for having given a well-founded hope - the green revolution.

The emergence of genetic engineering techniques led to the first genetically modified organisms (GMO's) to be developed and released for commercial use in the mid-1990s. The first wave of such crops, mainly utilizing popular row crops such as corn, soybeans, and cotton, to add new traits such as insect resistance and pesticide resistance through the insertion of genetic material from other organisms, most commonly the bacillus thuringiensis (BT) bacterium. More recently, new techniques have been developed to enable editing DNA segments of individual crops themselves, by turning on or shutting off certain genes that already exist within specific organisms. These techniques, known as CRISPR or CAS9, recently won recognition through the awarding of the 2020 Nobel Prize for chemistry to their developers, Dr. Emmanuelle Charpentier from the Max Planck institute in Germany and Dr. Jennifer Doudna from U.C.-Berkeley.

For the last decade or so, plant scientists around the world have been working on ways to improve the photosynthetic process itself, by improving the efficiency with which plants convert water, sunlight, and carbon dioxide into plant growth. Much of that work is taking place through the RIPE project (Realizing Increased Photosynthetic Efficiency) headquartered at the University of Illinois, funded primarily by the Bill and Melinda Gates Foundation, the Foundation for Food and Agriculture Research (FFAR), and the U.K.s Foreign Commonwealth and Development Office (formerly the Department for International Development, or DFID). In research published in 2019, efforts to engineer alternate pathways to refine the photosynthesis process were found to drastically shorten the trip and save enough resources to boost plant growth by 40 percent. This is the first time that an engineered photorespiration fix has been tested in real-world agronomic conditions. Other work is underway at a consortium of universities to develop rice varieties that use the more efficient C4 photosynthesis pathway such as is found in corn and sugarcane, eschewing the less efficient C3 pathway that rice plants currently utilize. A November 2020 article described their current work, which involved assembling five genes from maize that code for five enzymes in the C4 photosynthetic pathway into a single gene construct and installing it into rice plants.

Original post:
The History of Plant Breeding--Improving on Nature? - Agweb Powered by Farm Journal

Amid the devastating Covid-19 pandemic, two researchers are proposing a drastic way to stop future pandemics: using a technology called a gene drive to rewrite the DNA of bats to prevent them from becoming infected with coronaviruses.

The scientists aim to block spillover events, in which viruses jump from infected bats to humans one suspected source of the coronavirus that causes Covid. Spillover events are thought to have sparked other coronavirus outbreaks as well, including SARS-1 in the early 2000s and Middle East respiratory syndrome (MERS).

This appears to be the first time that scientists have proposed using the still-nascent gene drive technology to stop outbreaks by rendering bats immune to coronaviruses, though other teams are investigating its use to stop mosquitoes and mice from spreading malaria and Lyme disease.

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The scientists behind the proposal realize they face enormous technical, societal, and political obstacles, but want to spark a fresh conversation about additional ways to control diseases that are emerging with growing frequency.

With a very high probability, we are going to see this over and over again, argues entrepreneur and computational geneticist Yaniv Erlich of the Interdisciplinary Center Herzliya in Israel, who is one of two authors of the proposal, titled Preventing COVID-59.

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Maybe our kids will not benefit, maybe our grandchildren will benefit, but if this approach works, we could deploy the same strategy against many types of viruses, Erlich told STAT.

As the Covid-19 pandemic has killed more than 3.9 million people and triggered $16 trillion in economic losses, scientists, public health officials, ecologists, and many others have called for deeper investments in longstanding pandemic prevention measures.

Such measures include boosting global health funding, reducing poverty and health inequity, strengthening disease surveillance networks and community education, preventing deforestation, controlling the wildlife trade, and beefing up investments in infectious disease diagnostics, treatments, and vaccines.

Erlich and his co-author, immunologist Daniel Douek at the U.S. National Institute of Allergy and Infectious Diseases, now propose an additional measure: creating a gene drive to render wild horseshoe bats immune to the types of coronavirus infections that are thought to have triggered the SARS, MERS, and Covid-19 pandemics. They shared the proposal Wednesday on the Github publishing and code-sharing platform.

Though there is heated debate about whether the Covid-19 virus originated in a lab, most scientists say the virus is most likely to have originated in wild animals. There is strong evidence, for instance, that horseshoe bats carry the coronavirus that caused the SARS outbreak.

A gene drive is a technique for turbocharging evolution and spreading new traits throughout a species faster than they would spread through natural selection. It involves using a gene editing technology such as CRISPR to modify an organisms genome so that it passes a new trait to its offspring and throughout the species.

The idea of making a gene drive in bats faces such enormous scientific, technical, social, and economic obstacles that scientists interviewed by STAT called it folly, far-fetched, and concerning. Among other objections, they worried about unintended consequences with so radically tampering with nature.

We have other ways of preventing future Covid-19 outbreaks, argued Natalie Kofler, a trained molecular biologist and bioethicist and founder of Editing Nature, a group focused on inclusive decision-making about genetic technologies.

We need to be thinking about changing the unhealthy relationship of humans and nature, not to gene drive a wild animal so that we can continue our irresponsible and unsustainable behavior that is going to come back to bite us in the ass in the future.

Coming from anyone else, the idea might be laughed off.

But Erlich has a reputation as a visionary. In 2014, for instance, he and another scientist predicted that genetic genealogy databases might one day be used to reveal peoples identities. Four years later, that happened, when law enforcement officials used the method to identify a former California police officer as the notorious Golden State Killer. Erlich has since become chief scientific officer of the genetic genealogy company MyHeritage and he is also founder of a biotech startup, Eleven Therapeutics.

Now, Erlich says, its worth thinking about how a gene drive could work in bats.

Erlich proposes to modify bat genomes so that they would block coronavirus infections. He would create a genetic element, called a shRNA, that targets and destroys coronaviruses. He would then use CRISPR to insert this element into the bat genome. The insertion would also contain a component that pushes bats to preferentially pass the shRNA to their offspring, so that entire bat populations would soon resist coronavirus infection.

Its almost like creating a self-propagating vaccine in these bats, Erlich said.

The idea is intriguing, said geneticist and molecular engineer George Church of the Wyss Institute for Biologically Inspired Engineering at Harvard University.

Most of the proposals Ive heard involving gene drives have seemed quite attractive, and this is probably the most attractive, he said.

Creating a gene drive in bats would be enormously difficult, and perhaps impossible, other scientists say. Researchers have created gene drives in mosquitoes and mice in the lab, but none has been released in the wild. The most advanced gene drive projects intended for field use involve modifying mosquitoes to prevent the spread of malaria and attempting to engineer mice to stop them from causing ecological damage.

But its been difficult to engineer effective gene drives in mammals. Developmental geneticist Kim Cooper and her team at the University of California, San Diego, engineered a gene drive that spread a genetic variant through 72% of mouse offspring in her lab. That isnt efficient enough to quickly spread the desired trait in the wild.

Whats more, creating a gene drive in bats would be much harder than it is in mice, because bat researchers lack the genetic tools available in mice, said Paul Thomas, a developmental geneticist at the University of Adelaide in Australia, who is trying to engineer mouse gene drives.

And unlike mice, which can breed at 6 to 8 weeks of age, bats take two years to reach sexual maturity, so it would take much longer for a trait to spread throughout wild bat populations than in lab mouse populations.

They say the proposal is not an easy feat from a technical standpoint, and I think that underplays how hard it might be, Cooper said.

Biologists also say that Erlichs proposal is unlikely to work in the wild even if researchers get bat gene drives to work in a lab because bats are incredibly diverse.

There are 1,432 bat species, including multiple horseshoe bat species that carry coronaviruses and pass them among each other.

Wild viruses similar to the human Covid-19 virus have been found in bats across Asia, and in pangolins. And in June, Weifeng Shi of the Shandong First Medical University & Shandong Academy of Medical Sciences in Taian, China, found 24 coronavirus genomes in bat samples taken from in and around a botanical garden in Yunnan province, in southern China.

Engineering one gene drive in just one bat species would not solve the problem, biologists say.

Youd have to develop systems for entire bat communities, said evolutionary biologist Liliana Dvalos of Stony Brook University. Its the job of visionaries to come up with creative ideas, but this is a giant blind spot in their thinking.

Biologists are also concerned about focusing on bats themselves, because they may not be the most important source of human epidemics. No one has found the exact bat analog to the human Covid-19 virus, or definitively pro
ven that spillover from bats did start the pandemic. Coronaviruses have also been found in other species, including palm civets, pangolins, and camels.

Further, nobody knows how eliminating coronaviruses might affect bats.

We dont know the implications of wiping out coronaviruses in bat populations, because we dont know how bats have evolved to coexist with these viruses, said virologist Arinjay Banerjee of the Vaccine and Infectious Disease Organization at the University of Saskatchewan in Saskatoon, Canada.

Some scientists, though, welcomed Erlichs proposal, hoping that it will focus attention on what it would take to create successful mammalian gene drive systems.

Royden Saah, for instance, coordinates the Genetic Biocontrol of Invasive Rodents (GBIRd) program, which is trying to engineer gene drives in mice to prevent island bird extinctions. He wants to see more funding to help scientists solve the technical obstacles to such projects, and involve more communities in discussions about these ideas.

I would be concerned if this proposal detracted from the need to fund public health infrastructure, said Saah. But with that caveat, he added, I think this proposal could make people think, OK, if we were to use this technology in this animal in this system, what would we need to do? There would need to be a foundation of ethical development, of clear understanding, of social systems and trust, and technology built in a stepwise manner.

Virologist Jason Kindrachuk of the University of Manitoba said that there are numerous technical and political challenges to a bat gene drive project, and that preventing future outbreaks should mainly involve tackling the challenges that drive spillover events, such as underfunded public health systems, poverty, food insecurity and climate-change-driven ecological disruption. But, he said, given the enormous economic and human toll of Covid-19 and other recent outbreaks, scientists and public health officials might also need to consider new approaches.

In the past, maybe we were blinded a little bit by our belief that we would just be able to increase surveillance and identify these pathogens prior to them spilling over, Kindrachuk said. We now realize that this is going to take a lot of different efforts, so theres an aspect from a research standpoint where we continue to look at things like this, and say, what are the top 5 to 10 things we should invest in.

Erlich acknowledges the obstacles to his proposal, but thinks they arent insurmountable. He thinks the project would require an international investment involving a multidisciplinary consortium.

While we totally agree about the technical complexities, technology advances at exponential rates, Erlich said. Things that are nearly impossible now can be totally reachable within a decade or so.

He also thinks a gene drive could be a better alternative than culling bats, which has been tried (unsuccessfully) in communities around the world, and that scientists could monitor for negative impacts on bat populations.

Lets discuss the idea and think about what we can do to identify a very rigorous and cautious way to test this approach, Erlich said. We dont like to mess with nature, but the current situation is not sustainable.

Excerpt from:
Could editing the genomes of bats prevent future pandemics? - STAT - STAT

For Baric, that research started in the late 1990s. Coronaviruses were then considered low risk, but Barics studies on the genetics that allowed viruses to enter human cells convinced him that some might be just a few mutations away from jumping the species barrier.

That hunch was confirmed in 200203, when SARS broke out in southern China, infecting 8,000 people. As bad as that was, Baric says, we dodged a bullet with SARS. The disease didnt spread from one person to another until about a day after severe symptoms began to appear, making it easier to corral through quarantines and contact tracing. Only 774 people died in that outbreak, but if it had been transmitted as easily as SARS-CoV-2, we would have had a pandemic with a 10% mortality rate, Baric says. Thats how close humanity came.

As tempting as it was to write off SARS as a one-time event, in 2012 MERS emerged and began infecting people in the Middle East. For me personally, that was a wake-up call that the animal reservoirs must have many, many more strains that are poised for cross-species movement, says Baric.

By then, examples of such dangers were already being discovered by Shis team, which had spent years sampling bats in southern China to locate the origin of SARS. The project was part of a global viral surveillance effort spearheaded by the US nonprofit EcoHealth Alliance. The nonprofitwhich has an annual income of over $16 million, more than 90% from government grantshas its office in New York but partners with local research groups in other countries to do field and lab work. The WIV was its crown jewel, and Peter Daszak, president of EcoHealth Alliance, has been a coauthor with Shi on most of her key papers.

By taking thousands of samples from guano, fecal swabs, and bat tissue, and searching those samples for genetic sequences similar to SARS, Shis team began to discover many closely related viruses. In a cave in Yunnan Province in 2011 or 2012, they discovered the two closest, which they named WIV1 and SHC014.

Shi managed to culture WIV1 in her lab from a fecal sample and show that it could directly infect human cells, proving that SARS-like viruses ready to leap straight from bats to humans already lurked in the natural world. This showed, Daszak and Shi argued, that bat coronaviruses were a substantial global threat. Scientists, they said, needed to find them, and study them, before they found us.

Many of the other viruses couldnt be grown, but Barics system provided a way to rapidly test their spikes by engineering them into similar viruses. When the chimera he made using SHC014 proved able to infect human cells in a dish, Daszak told the press that these revelations should move this virus from a candidate emerging pathogen to a clear and present danger.

To others, it was the perfect example of the unnecessary dangers of gain-of-function science. The only impact of this work is the creation, in a lab, of a new, non-natural risk, the Rutgers microbiologist Richard Ebright, a longtime critic of such research, told Nature.

To Baric, the situation was more nuanced. Although his creation might be more dangerous than the original mouse-adapted virus hed used as a backbone, it was still wimpy compared with SARScertainly not the supervirus Senator Paul would later suggest.

In the end, the NIH clampdown never had teeth. It included a clause granting exceptions if head of funding agency determines research is urgently necessary to protect public health or national security. Not only were Barics studies allowed to move forward, but so were all studies that applied for exemptions. The funding restrictions were lifted in 2017 and replaced with a more lenient system.

If the NIH was looking for a scientist to make regulators comfortable with gain-of-function research, Baric was the obvious choice. For years hed insisted on extra safety steps, and he took pains to point these out in his 2015 paper, as if modeling the way forward.

The CDC recognizes four levels of biosafety and recommends which pathogens should be studied at which level. Biosafety level 1 is for nonhazardous organisms and requires virtually no precautions: wear a lab coat and gloves as needed. BSL-2 is for moderately hazardous pathogens that are already endemic in the area, and relatively mild interventions are indicated: close the door, wear eye protection, dispose of waste materials in an autoclave. BSL-3 is where things get serious. Its for pathogens that can cause serious disease through respiratory transmission, such as influenza and SARS, and the associated protocols include multiple barriers to escape. Labs are walled off by two sets of self-closing, locking doors; air is filtered; personnel use full PPE and N95 masks and are under medical surveillance. BSL-4 is for the baddest of the baddies, such as Ebola and Marburg: full moon suits and dedicated air systems are added to the arsenal.

There are no enforceable standards of what you should and shouldnt do. Its up to the individual countries, institutions, and scientists.

In Barics lab, the chimeras were studied at BSL-3, enhanced with additional steps like Tyvek suits, double gloves, and powered-air respirators for all workers. Local first-responder teams participated in regular drills to increase their familiarity with the lab. All workers were monitored for infections, and local hospitals had procedures in place to handle incoming scientists. It was probably one of the safest BSL-3 facilities in the world. That still wasnt enough to prevent a handful of errors over the years: some scientists were even bitten by virus-carrying mice. But no infections resulted.

In 2014, the NIH awarded a five-year, $3.75 million grant to EcoHealth Alliance to study the risk that more bat-borne coronaviruses would emerge in China, using the same kind of techniques Baric had pioneered. Some of that work was to be subcontracted to the Wuhan Institute of Virology.

Read the original:
Inside the risky bat-virus engineering that links America to Wuhan - MIT Technology Review

The Department of Theatre and Dance and Catalyst: A Theatre Think Tank, a launching pad for new works, raise the remote curtain this week on two productions examining diverse contemporary themes.

Jonathan Luskin, whose Kill the Wabbit was workshopped at UC Davis in 2018, is back with Perfect, three interwoven stories exploring the boundless desire for flawless children and the impossibility of objectively defining what that means.

Perfect

A Bee in a Jar

Catalyst productions may contain adult situations and language.

Six actors portray 13 characters, including a cell biologist and her brilliant, wheelchair-using son who discover their research is being used to clean disabilities from the human genome; and a young couple who turn to an app to design the perfect child. They will present the play as an informal reading at 6 p.m. Wednesday (Feb. 17).

Perfectis directed by alumnaJanLee Marshall(M.F.A, dramatic art, 15) and features actor Danny Gomez, recipient of the 2020 Media Access Award, which recognizes depictions of disability that are accurate, inclusive and multifaceted. The cast also includes undergraduate students Sophie Brubaker, Cheryl Kuo, Kyle Nagasawa and Aubrey Schoeman. Undergraduate student Sam Votrian is the stage manager.

In A Bee in a Jar by Andrew Nichols, three men with very different temperaments try to figure out why they were seized a month earlier and locked together in a featureless room. The play will be performed at 6 p.m. Friday and Saturday (Feb. 19 and 20).

Nicholls is a television writer and author who has worked on The Tonight Show and numerous Nickelodeon shows. He is the author of the recently published Comedy Writer: Craft Advice From a Veteran of Sitcoms, Sketch, Animation, Late Night, Print and Stage Comedy. His play {LOVE/logic} was staged at UC Davis in 2019.

Theatre and television actor Laura Hall, who appeared on Broadway in Wonderland and in the national tour of the revival of Pippin, is the director. She has recently relocated from New York to Sacramento County.

The cast includes alumni Jordan Brownlee (B.A., cinema and digital media, 20), Nate Challis (B.A., theatre and dance, 20) and Noah VanderVeer-Harris (B.A., theatre and dance, 20), as well as undergraduate studentsErolina Kamburova andHailey Peterson. Undergraduate studentShachar-Lee Yaakobovitz is the stage manager.

As a virtual new works festival this year, Catalysts online process allows actors and creative teams to collaborate from various locations across time zones.

Broadway veteran Mindy Cooper, professor of theatre and dance, and Lisa Quoresimo (Ph.D., performance studies, 18) are co-founders of Catalyst.

The Department of Theatre and Dance is producing the 2020-21 Catalyst season with support from the Jan Shrem and Maria Manetti Shrem Museum of Art, Bike City Theatre Company, Southern Utah University and San Francisco Youth Theatre.

Follow Dateline UC Davis on Twitter.

Original post:
2 Plays From Catalyst: A Theatre Think Tank - UC Davis

Global CRISPR and CAS GeneMarket, By Product Type (Vector-based Cas and DNA-free Cas), By Application (Genome Engineering, Disease models, Functional Genomics, Knockdown/activation, and Other Applications), By End User (Biotechnology and Pharmaceutical Companies,Academic Government Research Institutes, and Contract Research Organizations), and By Region (North America, Latin America, Europe, Asia Pacific, Middle East, and Africa) was valued at US$ 1,388.1 million in 2017, and is projected to exhibit a CAGR of 20.8% over the forecast period (2018 2026).

Manufacturers in the CRISPR and CAS gene are collaborating with many companies for sponsoring clinical trials. Editas Medicine has licensed CRISPR and other gene editing patent rights from the Broad Institute, the Massachusetts Institute of Technology (MIT), Harvard University, and others. In March 2017, Editas reportedly entered into an agreement with Irish pharmaceutical company Allergan under, which Editas was to receive a US$ 90 million up-front payment for an option to license up to five preclinical programs targeting eye disease. Moreover, various organizations are also focusing on new clinical trials for the CRISPR and CAS gene for cancer treatment. In 2018, CRISPR Therapeutics and Vertex launched the first in-human clinical trial of CRISPR genome editing technology sponsored by U.S. companies. The trial is testing an experimental therapy for the blood disorder -thalassemia in Regensburg, Germany.

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Increasing research and studies regarding the CRISPR and CAS gene technology is majorly driving the growth of CRISPR and CAS gene market. In 2017, Editas partnered with Juno Therapeutics for cancer-related research using CRISPR. Under the terms of the agreement, Juno had to pay Editas an initial payment of US$ 25 million, in which up to US$ 22 million will be used in research support for three programs over five years. Editas has also engaged in a three-year research and development (R&D) collaboration deal with San Raffaele Telethon Institute for Gene Therapy to research and develop next generation stem cell and T-cell therapies for the treatment of rare diseases.

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CRISPR and CAS Gene Market to Score Past US$ 7603.8 Million Valuation by 2027: CMI KSU | The Sentinel Newspaper - KSU | The Sentinel Newspaper

The Mutant Project: Inside the Global Race to Genetically Modify Humansby Eben Kirksey. St. Martins Press, November 2020. Excerpt previously published by Black Inc.

Surreal artwork in the hotel lobbya gorilla peeking out of a peeled orange, smoking a cigarette; an astronaut riding a cyborg giraffewas the backdrop for bombshell news rocking the world. In November 2018, Hong Kongs Le Mridien Cyberport hotel became the epicenter of controversy about Jiankui He, a Chinese researcher who was staying there when a journalist revealed he had created the worlds first edited babies. Select experts were gathering in the hotel for the Second International Summit on Human Genome Editinga meeting that had been called to deliberate about the future of the human species. As CNN called the experiment monstrous, as heated discussions took place in labs and living rooms around the globe, He sat uncomfortably on a couch in the lobby.

He was trying to explain himself to Jennifer Doudna, the chemist at UC Berkeley, who is one of the pioneers behind CRISPR, a new genetic-engineering tool. Doudna had predicted that CRISPR would be used to direct the evolution of our species,* writing, We possess the ability to edit not only the DNA of every living human but also the DNA of future generations. As He went through his laboratory protocol, describing how he had manipulated the genes of freshly fertilized human eggs with CRISPR, Doudna shook her head. She knew that this moment might be coming someday, but she imagined that it would be in the far future. Amid the bustle of hotel guests, science fiction began to settle into the realm of established fact.

St. Martins Publishing Group

I was checking in to Le Mridien as the story broke and first heard rumors about Hes babies while chatting in the elevator with other summit delegates. We had come to Hong Kong to discuss the science, ethics, and governance of CRISPR and an assortment of lesser-known tools for tinkering with DNA. Struggling to overcome intense jet lagfresh off planes from Europe, the United States, and other parts of Asiawe listened to speculation in the hotels hallways while swimming through reality, caught between waking and dreaming.

Opening the door to my hotel room, a luxury suite courtesy of the U.S. National Academy of Sciences, I hunted for reliable sources of information online. I had been invited to speak on the research ethics panel, after Jiankui He, so I needed to play catch-up, fast. I found YouTube videos posted by Hes lab just hours before, offering details of the experiment. Posing in front of his laboratory equipment, with a broad smile on his face, He announced to the world: Two beautiful little Chinese girls, named Lulu and Nana, came crying into this world as healthy as any other babies a few weeks ago. The experiment aimed to delete a single gene with CRISPR. This new technique of genetic surgery, He claimed, could produce children who were resistant to the HIV virus.

Hunched over the glowing screen of my laptop, I perused the opinions that were just starting to form. Chinese media pundits suggested that a Nobel Prize might be in the making, saying that He was following in the footsteps of scientists who produced the first controversial test-tube baby in 1978. A raucous debate was taking place on WeiboChinas prominent social media platformas 1.9 billion people viewed the hashtag # (#FirstGeneEditedHIVImmuneBabies). Some Chinese influencers were praising Jiankui He as a national scientific hero. Others condemned him, saying that it was shameful to treat children like guinea pigs. Journalists were starting to discover Dr. Hes ties to biotechnology companiesone reportedly worth US$312 millionand alleged that there were serious financial conflicts of interest.

Anyone who follows the news knows the basic story. Over the next few days, Jiankui He experienced a meteoric rise to fame, followed by a dramatic fall from grace. Eventually, he lost his university job and was thrown in jail. A district court in China sentenced him to three years in prison for practicing medicine without a license, denouncing his pursuit of personal fame and profit.

Dr. Hes story is a gateway into a much bigger enterprise: the tale of CRISPR and the emergence of genetic medicine. The gala was quietly abuzz with news of other efforts to genetically modify humans. Experiments were already underway in England, the United States, and many other labs in mainland China. As billionaires and Wall Street investors were getting in on the action, as scientists and doctors were making careers out of CRISPR, I wondered: Who counts as a visionary, and who becomes a pariah?

He spoke about his gene-editing experiment that led to the birth of twin girls while at a summit in Hong Kong in 2018. VOAIris Tong/Wikimedia Commons

He was not alone in the pursuit of fame and fortune. It seemed like none of the scientists at the gala were innocent of financial conflicts of interest. Collectively, these enterprising biologists had already raised hundreds of millionsfrom venture capitalists, big pharma companies, and the stock marketfor genetic engineering experiments in human patients. I overheard excited chatter about new investment opportunities. The first gene therapy, a cancer treatment, had recently been approved in the United Stateswith a US$475,000 price tag. While the scientists gushed about the CRISPR revolution, I was quietly thinking about how genetic medicine is producing other upheavals in society. Profit-driven ventures in research and medicine were producing a new era of dramatic medical inequality.

As market forces propelled CRISPR into the clinic, I set out to answer basic questions about science and justice: Who is gaining access to cutting-edge genetic medicine? Are there creative ways to democratize the field? Panning out, I also explored questions that could have profound implications for the future of our species: Should parents be allowed to choose the genetic makeup of their children? How much can we actually change about the human condition by tinkering with DNA?

As a cultural anthropologist, I have often found myself opposing biologists in debates about human nature. Ever since Margaret Mead wrote her 1928 classicComing of Age in Samoa, anthropologists have argued that a persons life is shaped by the social environment in which each is born and raised rather than genetic heredity alone.Anthropologists have recently joined other progressive thinkers to imagine how science has enabled new experimental possibilities for human beings.Now we are studying how the human social environment has been shaped by synthetic chemistry, smartphones, the internet, and biotechnology.

My goal has been to map how genetic engineering will transform humanity. Rather than limit my research to a single culture, I followed CRISPR around the globe. I tracked the impact of this gene-editing tool as it traveled from media reports to laboratories, through artificial intelligence algorithms, and into the cells of embryos and the bodies of living people. Using an anthropological lens, I examined new forms of power as scientists, corporate lobbyists, medical doctors, and biotechnology entrepreneurs worked to redesign life itself.

I will offer you a mosaic portrait. This is a story of people and concerns on either side of the dynamics of power that has emerged with CRISPR. I moved among the powerful in their native habitats: conferences, fancy hotels, restaurants, corporate offices, and cluttered labs. To understand how social inequality is changing in this brave new world, I also interviewed chronically ill patients, disabled scholars, and hackers. From the power centers to the margins, I went where I could find answers. Very old conflicts were playing out even as new technologies transformed science and medicine.

An exhibit on reproductive technologies at the China National GeneBank envisions a future where robots rear human embryos. Eben Kirksey

When I set out to meet some of the first genetically modified people, I f
ound activists who were battling insurance agents and biotechnology companies for potentially lifesaving treatments. Nearly a decade before Dr. He stirred up controversy in China, a small group of HIV-positive gay men in the United States quietly participated in a clinical trial dubbed the first-in-man gene-editing experiment. Researchers aimed to delete a gene from these menthe same DNA sequence later targeted by Hein hopes of engineering resistance to the virus and repairing damage to their immune systems from AIDS. One veteran HIV activist who participated in this study, Matt Sharp, convinced me that having his DNA altered wasnt a big deal and that genetic engineering does indeed have real medical promise. Sharp also confirmed my suspicions: Biotech companies are putting profits ahead of human health as they search for lucrative applications of gene editing in the clinic.

Gene editing is not a particularly good metaphor for explaining the science of CRISPR. With a computer, I can easily cut and paste text from one application to another, or make clean deletionsletter by letter, line by line. But CRISPR does not have these precise editorial functions. CRISPR is more like a tiny Reaper drone that can produce targeted damage to DNA. Sometimes it makes a precision missile strike, destroying the target. It can also produce serious collateral damage, like a drone attack that accidentally takes out a wedding party instead of the intended target. Scientists often accidentally blast away big chunks of DNA as they try to improve the code of life. CRISPR can also go astray when the preprogrammed coordinates are ambiguous, like a rogue drone that automatically strikes the friends, neighbors, and relatives of suspected terrorists. CRISPR can persist in cells for weeks, bouncing around the chromosomes, producing damage to DNA over and over again every time it finds a near match to the intended target.

How much can we actually change about the human condition by tinkering with DNA?

It is important to signal a sense of risk or a need for caution in using CRISPR. Other metaphorslike genetic surgery or DNA hackinghave been proposed to replace the idea of editing. The idea of genetic surgery suggests that there can be a slip of the surgeons knife, creating an unintended injury. Each of these imagesthe targeted missile, the surgeons scalpel, the hackers codeoffers a perspective on how CRISPR works, even while concealing messy cellular dynamics. In the absence of a perfect metaphor, ultimately, I think that technical language describes it best: CRISPR is an enzyme that produces targeted mutagenesis.

In other words, CRISPR generates mutants.

Strictly speaking, we are all mutants. At a molecular level, each of us is unique. Each of us starts life with 4080 new mutations that were not found in our parents. From birth, each of us has around 20 inactive genes from loss-of-function mutations. During the course of a normal human life, we also accumulate mutations in our bodies, even in our brains. By the time we reach age 60, a single skin cell will contain between 4,000 and 40,000 mutations, according to a study in theProceedings of the National Academy of Sciences. These genetic changes are the result of mistakes made each time our DNA is copied during cell division or when cells are damaged by radiation, ultraviolet rays, or toxic chemicals. Generally, mutations arent good or bad, just different.

Mutants in popular culture play important roles in our high-tech myths. Some cartoons simply celebrate mutation as whimsical possibility. The pizza-eating Teenage Mutant Ninja Turtles are known for fighting crime in support of established law and order. Darker speculative fiction uses mutants to illustrate the hypocrisy and inhumanity of the scientific establishment. Violent experiments on children who were born with special abilities feature in recent Netflix series likeStranger Things. Horror flicks and video games featuring mindless zombies and flesh-eating mutants have a common theme: Science could create monsters that cannot be controlled.

Reporters who sounded the alarm about Lulu and Nanas birthcalling them freaky CRISPR Frankenbabiesclearly had not done their literary homework. Frankensteins monster is now popularly imagined as a dimwitted giant with electrodes in his neckfollowing imagery from the first black-and-white film, put out by Universal Pictures in 1931. The originalFrankenstein, Mary Shelleys gothic novel from 1818, described a superhuman creature that was driven by the desire to be loved. The highly intelligent, articulate, and high-minded creature only turned violent when he was shunned by human society. Amid the controversy about Dr. Hes experiment, a political theorist and literary scholar named Eileen Hunt Botting defended the rights of genetically modified children to live, love, and flourish. Flipping the mainstream script, she wrote an essay for TheWashington Postsuggesting that Frankenstein is an apt cautionary tale about the possibility of devastating discrimination against a bioengineered child.

Some media reports on Lulu and Nana, the first known gene-edited human babies, referenced the science-fiction character Frankenstein (shown here from the film by that name). Universal Pictures/Wikimedia Commons

During my international adventures in the world of CRISPR research, I kept science fiction classics close at hand. The rich archive of speculative fiction has helped me understand the perils and potential of experiments that are remaking the human species.

Scientists have identified some geneslike those associated with eye and skin colorthat would be relatively easy to manipulate. One Russian American gene-editing expert, Fyodor Urnov, intimated that it should be biologically possible to engineer soldiers or athletes with enhanced endurance, speed, and muscle mass. Genetic enhancements come with serious health risks, but military leaders have a long history of ignoring the health and well-being of their soldiers. Fertility clinics also have a bad track record as profit-driven enterprises, ready to sell couples expensive and scientifically unproven treatments. The New Hope Fertility Center in Manhattan is already advertising a new technique: Couples could soon have the opportunity to create designer babies with CRISPR.As scientists speculate about post-racial futures and nightmare military scenarios, as market forces bring new genetic technologies into the clinic at a dizzying speed, it is time to slow down and establish some clear rules for the road. Misguided attempts to improve the human species have already produced atrocitieslike the Nazi death camps that systematically eliminated homosexuals and Jews from the population. In the wrong hands, CRISPR could have devastating consequences for humanity.

This excerpt has been edited slightly for style and length.

* Clarification: This quote comes from A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution, written by Jennifer Doudna and Samuel Sternberg.

See the rest here:
CRISPR Mutants - The Dawn of CRISPR Mutants - SAPIENS - SAPIENS

Introduction

Heterogeneous drug response is the major hurdle in the successful treatment of diseases, which is due to genetic variations in the drug metabolizing enzyme genes. Knowledge of allelic frequency distribution of drug metabolizing enzymes within populations can be useful to identify risk groups for adverse drug reaction and to optimize drug doses. It can be utilized to select representative populations in clinical trials. The cytochrome P450 (CYP) family is an important enzyme of ADME (related to absorption, distribution, metabolism and excretion of drug) genes, of which CYP2C9 is the major constituent of CYP2C subfamily in the human liver. It metabolizes a wide range of drugs including anticoagulant (warfarin), nonsteroidal anti-inflammatory (celecoxib, diclofenac), antidiabetic (nateglinide, tolbutamide), antihypertensive (irbesartan, losartan) and anti-epileptic (phenytoin).1 Several variations in CYP2C9 have been reported, which affect metabolism of the drug. Most notable variations are CYP2C9*2 (R144C) and CYP2C9*3 (I359L), which significantly decreases enzyme activity.2 Interestingly, these variations are highly heterogeneous among world population; (1) 819% and 3.316.3% in Caucasian; (2) 00.1% and 1.13.6% in Asian; (3) 2.9% and 2.0% in African-American; and (4) 04.3% and 02.3% in Black/African, respectively.3 In addition, other rare and functionally relevant variations were also reported in various populations, which includes; (1) CYP2C9*6, 0.6% frequency in African-Americans;4 (2) CYP2C9*4, 0.5% in African-Americans and 6% in Caucasians;2,5 and (3) CYP2C9*13, 0.190.45% in Asian.6 Dai et al reported several rare variants in the Han Chinese population.7

Several studies have been performed on CYP2C9 in Indian populations. However, most of studies have focused only on CYP2C9*3 and CYP2C9*2 variants. Grik et al observed CYP2C9*3 only in the Indo-European population (0.381.85%), whereas it was absent in Dravidian, Austroasiatic and Tibeto-Burman populations.8 Indian populations are well known for their genetic diversity and practice of endogamy, hence they are expected to have high frequency of homozygous allele9. Many studies have shown that the variations in CYP2C9 are associated with therapeutic heterogeneity in Indian populations. CYP2C9*2 and *3 has been reported with less hydroxylation (or metabolism) of phenytoin in vivo in South Indian populations,10 compared to wild type CYP2C9*1. Ramasamy et al reported phenytoin toxicity in a patient with normal dose of 300 mg/day, who had CYP2C9*3/*3 genotype.11 The same symptoms were also reported by Thakkar et al in South Indian populations.12 Both of these drugs are metabolized by CYP2C9. Some of the drugs, metabolized by CYP2C9 have narrow therapeutic index eg warfarin, phenytoin, and tolbutamide. This is the reason that small change in the metabolizing activity of CYP2C9 may cause major changes in an individuals response against a drug. Considering this, we explored genetic diversity of functionally relevant variations of CYP2C9 within the Indian subcontinent and compared with other world populations. The outcome of this study may be useful to understand heterogeneous therapeutic response and development of personalized therapy for the populations of Indian subcontinent. Moreover, identification of South Asian-specific putative functional variants and associated haplotypes will open opportunity for further study.

A total of 1278 samples from 36 diverse Indian populations, in terms of ethnicity, linguistic and geographical locations, were included in this study (Table 1).9,13 Furthermore, 210 samples of South Asian origin were selected from our collection of whole genome/exome datasets. For comparison, 489 and 598 samples of South Asian origin were selected from the 1000 Genomes Project and GenomeAsia 100K Project, respectively.14,15 This work has been approved by the Institutional Ethical Committee of CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India. Informed written consent has been obtained from all the participants. The present study is conducted in accordance with the Declaration of Helsinki.

Ten milliliter intravenous blood samples of subjects were collected in an EDTA vacutainer, after obtaining informed written consent. Genomic DNA was extracted from whole blood, using the protocol described previously.16 These steps were followed for all samples which were subjected to either Sanger sequencing or next-generation sequencing (exome/genome).

All the nine exons, their respective intron-exon boundary, 3 and 5 UTR of CYP2C9 have been re-sequenced. For designing of primer, DNA sequence of ENST00000260682 from Ensembl (v75) has been used. Out of 3 mRNA of CYP2C9, only ENST00000260682 translate to protein. Primer3.0 web-based tool (http://simgene.com/Primer3) was used for designing the primers and further primers specificity were checked with NCBI-primer blast. The details of primer sequences are given in Supplementary Table 1. Polymerase chain reaction (PCR) was performed in 10.0 L volume, which contains 5.0 L of 2 EmeraldAmp GT PCR master mix, 10.0 ng of genomic DNA and 0.1 p mole (final concentration) of each primer. Thermal cycling conditions used are as follows: initial denaturation step of five minutes at 94C, followed by 35 cycles of denaturation step of 30 seconds. at 94C, annealing step of 30 seconds. at 55C, extension step of two minutes at 72C, followed by single step of final extension of seven minutes at 72C. PCR products were cleaned with Exo-SAP-IT (USB, Affymetrix, USA) with recommended protocol of the manufacturer. Cleaned PCR products (1.0 L) were subjected to sequencing using BigDye terminator (v3.1) cycle sequencing kit (Thermo Fisher Scientific, USA) and analyzed using ABI 3730XL DNA Analyzer. Sequences were edited and assembled using AutoAssembler (v1.0) software. Statistical analysis was performed using R packages. Gap package was used to calculate HWE equilibrium. The 95% confidence interval of allelic and genotypic percentage was calculated with ClopperPearson and SisonGlanz method using DescTools package of R. Surfer trial version (18.1.186) was used to interpolate frequency spectrum with Kriging gridding method and plots were generated using maps and spaMM package of R.

For whole genome and exome sequencing, libraries were prepared as per manufacturers protocol using Illumina Nextera DNA Flex Library Prep kit and Illumina TrueSeq DNA LP for enrichment kit, respectively. Sequencing of above library was performed on Illumina NovaSeq 6000 system. On an average of 30 and 100 coverage was generated for the whole genome and exome, respectively.

The sequencing data from all the samples was trimmed for adapters using Cutadapt (v2.7). The whole-genome datasets were aligned and processed to call variants using the pipeline of DRAGEN (v3.6.3), a Bio-IT platform for genome sequence data analysis. In case of whole-exome datasets, reads were aligned using the BWA tool (v0.7.10) and variants were called using the recommended pipeline of GATK4. The human reference genome version GRCh38 was used for the alignments of reads. The BCF tool was used to extract variants present in the CYP2C9. In the next step, all VCF files were combined with option CombineGVCFs of GATK. Variants were annotated using Variant Effect Predictor tool of Ensembl (v95.3). For phasing of the variants, PopgenPipeline Platform (PPP) was used with PHASE algorithm of BEAGLE. Novel haplotypes obtained in the current study are deposited to PharmVar (https://www.pharmvar.org/).

The A>C (rs1057910/CYP2C9*3) is a non-synonymous mutation, which replace isoleucine with leucine (ATT>CTT; Ile359Leu) and decreases enzyme activity. To explore the C allele frequency in Indian populations, initially we confirmed HardyWeinberg equilibrium (HWE). It was observed that 11 populations were not in HWE (p-value <0.01), which include one Indo-European population, Haryana Pandit (p-value=4.41106), one Austroasiatic, Gond (p-value=7.24108) and nine Dravidian populations; Mudaliar and Nadar from Tamil Nadu (p-val ue=1.971011 and 2.071012, respectively), Gawali from Karnataka (p-value=2.33105), Kurumba from Kerala (p-value=7.74106) and Thoti, Chenchu, Patkar and Vaddera from Andhra Pradesh (p-value=5.32104, 7.24108, 5.73107, 1.3105 and 4.67103, respectively) (Table 1).

Initially, we excluded those samples, which were not in HWE and estimated 9.51% (133 out of 1398) C allele in Indian populations, similar (p-value=0.286 and 0.2425) to South Asian populations of the 1000 Genomes Project (107 out of 978) and the GenomeAsia 100K Project (158 out of 1448) (Figure 1A). Further, we categorized samples on the basis of their linguistic affiliation and observed that Tibeto-Burman have lowest percentage of C allele (6.12%; 6 out of 98). Moreover, we observed 9.82% (44 out of 448), 8.41% (32 out of 380) and 9.88% (51 out of 516) of C allele frequency in Austro-Asiatic, Dravidian and Indo-European populations, respectively (Table 1). Interestingly, Tibeto-Burmans are insignificantly different (p-value=0.1127) from East Asians (27 out of 1001). Adi Dravidiars (scheduled caste) of Tamil Nadu, Ho (scheduled tribe) of Jharkhand and Baiswar (caste) of Uttar Pradesh have 17.857%, 15.385% and 16.176% of CYP2C9*3, respectively, which are higher in their respective linguistic group; while C allele is completely absent in Bhil of Gujarat, Raj-Gond of Madhya Pradesh and Chakesang Naga of Nagaland (Table 1). Our findings suggest that a high level of local heterogeneity exists in Indian subcontinent and we did not find any correlation with geographical distance (Figure 1B and Table 1). It is evident in the allele frequency map that Indian populations have a high frequency of CYP2C9*3, compared to other world populations (Figure 1A and Table 1). We observed a decreasing gradient of C allele frequency from the Indian subcontinent to Europeans (Figure 1A).

Figure 1 Geospatial frequency distribution of CYP2C9*3 and CYP2C9*3/*3. Genotypic and allelic frequency was interpolated with kriging method, and density map generated to explore geospatial frequency distribution. (A and C) represents the allelic (CYP2C9*3) and genotypic (CYP2C9*3/*3) distribution in world-wide population, while (B and D) represents distribution within South Asian populations. In (B and D), all samples from current study and the 1000 Genomes Project, present in HWE, were used in interpolation and represented as triangular and circle, respectively. It is evident in geospatial frequency map that South Asian populations have a high frequency of CYP2C9*3 and show high heterogeneity within the subcontinent. The same is true for CYP2C9*3/*3.

On the basis of founder events and longtime practice of endogamy, we have already predicted a high frequency of homozygous alleles in Indian populations.9,17 Since CYP2C9*3/*3 significantly decreases metabolic activity of enzymes compared to both CYP2C9*1/*3 and CYP2C9*1/*1, it would be interesting to explore genotype frequencies also in Indian populations. As expected, we observed a higher percentage (<5%) of CYP2C9*3/*3 among Indians, comparative to other world populations, who have 01% (Figure 1C and Table 2). Out of 21 populations of the 1000 Genomes Project, who lived outside the Indian subcontinent, only TSI (Italian populations) and CHS (South Chinese populations) have homozygous genotype (0.9 and 1%), while out of five populations who are living in the Indian subcontinent, three (PJL, ITU, and GIH) have 1% of CYP2C9*3/*3 (Table 2). Moreover, 1.25% South Asian samples of the GenomeAsia 100K project, were homozygous for the CYP2C9*3 allele. In the present study, we observed 05% CYP2C9*3/*3, of which Bhilala of Madhya Pradesh and Ho of Jharkhand have 5% and 3%, respectively; higher in Indo-Europeans and Austro-Asiatic linguistic groups (Table 2 and Figure 1D). We did not observe homozygous genotype CYP2C9*3/*3 in Tibeto-Burman as well as in Dravidian populations after excluding the populations, which were not in HWE (Figure 1D). In the NGS data repository, C allele was observed in 14.28% (60 out of 420). Out of 210 subjects, five (2.39%) and 50 (23.81%) were homozygous and heterozygous for the C allele, respectively.

Table 2 Distribution of CYP2C9*1 and *3 Genotype in Different Ethnic Populations.

A few rare nonsynonymous variants have also been observed in the current study. In 1278 samples, nonsynonymous C>T variant (rs28371685) which replaces the amino acid arginine with tryptophane (p.Arg335Trp) and determines the CYP2C9*11 haplogroup was found in three samples (one each in Chenchu, Telagas of Andhra Pradesh, and Mudliar of Tamil Nadu). Besides this, other functional variants rs1799853 (p.Arg144Cys) and rs72558189 (p.Arg335Trp) were observed in 10 and six samples of NGS data repository, respectively. These variants are associated with CYP2C9*2 and *14 haplotypes (Table 3).

Table 3 Rare Putative Functional Variants and Associated CYP2C9 Haplotypes

In total, eight rare and putative functional variants were not present in any reported CYP2C9 haplotypes. To determine the haplotypes, variants present within 3000 base-pair upstream and 250 base-pair downstream of CYP2C9 were utilized. In total, eight haplotypes were identified and annotation was obtained from PharmVar consortium (Table 3, Figure 2A and B). The haplotype CYP2C9*69 was identified in two subjects, CYP2C9*66 was identified in three subjects while other haplotypes were observed in only one subject. The nonsynonymous variants present in CYP2C9*63, *64, *65, *67 and *69 are predicted to be deleterious in both SIFT and Polyphen predictions. The p.Leu362Val present within CYP2C9*66 is predicted to be tolerated/benign. The Leu362 is present within hydrophobic substrate binding pocket of CYP2C9 and conversion from leucine to valine can affect assess of drug to the heme group of active site.24 A rare splice-site donor variant rs542577750 is present within CYP2C9*68 which can affect splicing of intron-7 (Figure 2B).

Figure 2 Distribution of variants in CYP2C9. (A) Rare and common putative functional variants observed in the current study. In total, 11 variants were nonsynonymous and one was splice donor variant. Other upstream and synonymous variants were used to determine haplotype of subjects. (B) Novel CYP2C9 haplotypes observed in current study.

In the Genome Aggregation Database project (gnomAD), rs578144976 and rs542577750 is reported only in South Asian samples (allele frequency=0.00085 and 0.00049). Moreover, the c.839C>G, c.978G>T, c.572A>G and c.1325G>T was not observed in any subjects of the gnomAD project. Besides South Asian subjects, the rs141489852 and rs776908257 was observed in American and non-Finnish European populations also. It suggests that CYP2C9*64, *65, *66, *68, *69 and *70 haplotypes are South Asian-specific.

CYP2C9 is highly expressed in the human liver and metabolizes a wide range of drugs. Several nonsynonymous mutations have been associated with less catalytic activity of CYP2C9 and intrinsic clearance of drugs. The CYP2C9*3 allele has been reported with hypersensitive reaction against phenytoin in epilepsy patients,18 and decreased metabolism of celecoxib.19 It was also reported with high incidence of response rate against sulfonamides, and urea derivatives.20 The in vitro studies suggest that CYP2C9*2 and CYP2C9*3 alleles reduce enzyme activity 2994% and 7191%, respectively, clearance rate of many drugs, which includes S-warfarin, tolbutamide, fluvastatin, glimepiride, tenoxicam, candesartan, celecoxib and phenytoin.21 Of which, S-warfarin, phenytoin and tolbutamide have a narrow therapeutic index and patients need the right amount of drug depending upon age, gender, and genetic make-up for successful treatment of disease. Moreover, homozygous mutations have more effect compared to heterozygous. The CYP2C9*3/*3 reduces 95% compared to 64% clearance rate by CYP2C9*1/*3.22 Considering the higher level of evidence of association between CYP2C9*3 and drug response, CPIC (Clinical Pharmacogenomics Implementation Consortium) categorized CYP2C9*3 under level-1A.23

Many studies have shown that the variations in CYP2C9 are assoc
iated with therapeutic heterogeneity in Indian populations. CYP2C9*2 and *3 have been reported with less hydroxylation (or metabolism) of phenytoin in vivo in South Indian populations,10 compared to wild type CYP2C9*1. Ramasamy et al reported phenytoin toxicity in a patient with normal dose of 300 mg/day, who had CYP2C9*3/*3 genotype.11 The same symptoms were also reported by Thakkar et al in South Indian populations.12 South Asians have a unique evolutionary history and have been practicing endogamy for many centuries, hence the high frequency of homozygous CYP2C9*3/*3 identified in the current study is not surprising. A similar trend was also observed in samples of the 1000 Genomes Project in which South Asians have high allelic and genotypic frequency of CYP2C9*3. Since CYP2C9*3/*3 has a more pronounced effect, we predict heterogeneous drug response in South Asians compared to other world populations. It would be interesting to find out if all South Asian populations have a high frequency of CYP2C9*3 and *3/*3 alleles. We explored the frequency distribution, but did not find any correlation with linguistic or geographical location. Some of the populations have a high frequency of CYP2C9*3, eg 35.7% of individuals from the Adi Dravidars have the CYP2C9*3 allele, while some of the populations have a low frequency of the CYP2C9*3 allele. Approximately 1428%, 036%, 032%, and 019% of individuals speaking Austro-Asiatic, Dravidian, Indo-European and Tibeto-Burman languages had the CYP2C9*3 allele. This suggests that South Asians are highly heterogeneous for this locus. Moreover, patients from Vysya, Mahli, Warli, Medari, Reddy, Ho, Baiswar, and Adi Dravidar populations, who have >20% individuals with CYP2C9*3 allele, should be genotyped for better treatment of disease. But this approach must be established first and its efficacy must be evaluated. We also find other rare haplotypes. Of which, three were already reported and eight were novel. Out of eight novel haplotypes, CYP2C9*64, *65, *66, *68, *69*70 and haplotypes are South Asian-specific as variants present within these haplotypes are reported only in South Asian subjects of the gnomAD project. All of the novel haplotypes are predicted to be deleterious and may have effects on protein function. It would be interesting to explore the effects of these novel haplotypes on the metabolic activity of CYP2C9 and find genetic association with therapeutic response in large samples.

In conclusion, we identified high genetic heterogeneity in CYP2C9 locus among South Asian populations. We observed higher frequency of CYP2C9*3 and CYP2C9*3/*3 alleles among South Asian populations, compared to populations from the rest of the world. The CYP2C9*3 has been associated with therapeutic response. Moreover, in the in vitro studies, the effect of CYP2C9*3/*3 allele was seen more pronounced compared to heterozygous and wild type homozygous genotype. As South Asians have a high frequency of CYP2C9*3, it would be interesting to explore the potential of CYP2C9*3 as marker for personalized therapy. Furthermore, it would be interesting to compare frequency of responder and nonresponder patients among populations and to find correlation with frequency spectrum of pharmacologically important variations. We also observed several nonsynonymous rare variants and novel haplotypes (CYP2C9*63-*70) in the present study. Of which, CYP2C9*64, *65, *66, *68, *69 and *70 haplotypes are South Asian-specific. The SIFT and PolyPhen algorithm predicts that these variants are deleterious and damaging. Therefore, individuals having CYP2C9 haplotypes with deleterious variants may have different metabolic activity compared to wild type. Collectively, our data provide fundamental knowledge of CYP2C9 genetic polymorphisms in South Asia, which could be relevant to further CYP2C9-related functional research and for personalized medicine.

We express our deepest condolence on the passing away of Mr Saurav Sharma. This work was supported by Council of Scientific and Industrial Research (CSIR), Government of India. Sheikh Nizamuddin was supported by ICMR JRF-SRF research fellowship. KT was supported by J C Bose Fellowship from Science and Engineering Research Board (SERB), Department of Science and Technology, Government of India (GAP0542). We thank Prof. Andrea Gaedigk for her help in submission of haplotypes to the PharmVar consortium.

The authors report no conflicts of interest in this work.

1. Miners JO, Birkett DJ. Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol. 1998;45(6):525538. doi:10.1046/j.1365-2125.1998.00721.x

2. Sullivan-Klose TH, Ghanayem BI, Bell DA, et al. The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics. 1996;6(4):341349. doi:10.1097/00008571-199608000-00007

3. Yasuda SU, Zhang L, Huang SM. The role of ethnicity in variability in response to drugs: focus on clinical pharmacology studies. Clin Pharmacol Ther. 2008;84(3):417423.

4. Kidd RS, Curry TB, Gallagher S, Edeki T, Blaisdell J, Goldstein JA. Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. Pharmacogenetics. 2001;11(9):803808. doi:10.1097/00008571-200112000-00008

5. Kimura M, Ieiri I, Mamiya K, Urae A, Higuchi S. Genetic polymorphism of cytochrome P450s, CYP2C19, and CYP2C9 in a Japanese population. Ther Drug Monit. 1998;20(3):243247. doi:10.1097/00007691-199806000-00001

6. Si D, Wang J, Zhang Y, Zhong D, Zhou H. Distribution of CYP2C9*13 allele in the Chinese Han and the long-range haplotype containing CYP2C9*13 and CYP2C19*2. Biopharm Drug Dispos. 2012;33(6):342345. doi:10.1002/bdd.1804

7. Dai DP, Xu RA, Hu LM, et al. CYP2C9 polymorphism analysis in Han Chinese populations: building the largest allele frequency database. Pharmacogenomics J. 2014;14(1):8592. doi:10.1038/tpj.2013.2

8. Giri AK, Khan NM, Grover S, et al. Genetic epidemiology of pharmacogenetic variations in CYP2C9, CYP4F2 and VKORC1 genes associated with warfarin dosage in the Indian population. Pharmacogenomics. 2014;15(10):13371354. doi:10.2217/pgs.14.88

9. Reich D, Thangaraj K, Patterson N, Price AL, Singh L. Reconstructing Indian population history. Nature. 2009;461(7263):489494. doi:10.1038/nature08365

10. Rosemary J, Surendiran A, Rajan S, Shashindran CH, Adithan C. Influence of the CYP2C9 AND CYP2C19 polymorphisms on phenytoin hydroxylation in healthy individuals from south India. Indian J Med Res. 2006;123(5):665670.

11. Ramasamy K, Narayan SK, Chanolean S, Chandrasekaran A. Severe phenytoin toxicity in a CYP2C9*3*3 homozygous mutant from India. Neurol India. 2007;55(4):408409. doi:10.4103/0028-3886.33300

12. Thakkar AN, Bendkhale SR, Taur SR, Gogtay NJ, Thatte UM. Association of CYP2C9 polymorphisms with phenytoin toxicity in Indian patients. Neurol India. 2012;60(6):577580. doi:10.4103/0028-3886.105189

13. Moorjani P, Thangaraj K, Patterson N, et al. Genetic evidence for recent population mixture in India. Am J Hum Genet. 2013;93(3):422438. doi:10.1016/j.ajhg.2013.07.006

14. Genomes Project C, Auton A, Brooks LD, et al. A global reference for human genetic variation. Nature. 2015;526(7571):6874.

15. GenomeAsia KC. The GenomeAsia 100K Project enables genetic discoveries across Asia. Nature. 2019;576(7785):106111.

16. Thangaraj K, Joshi MB, Reddy AG, Gupta NJ, Chakravarty B, Singh L. CAG repeat expansion in the androgen receptor gene is not associated with male infertility in Indian populations. J Androl. 2002;23(6):815818.

17. Nakatsuka N, Moorjani P, Rai N, et al. The promise of discovering population-specific disease-associated genes in South Asia. Nat Genet. 2017;49(9):14031407. doi:10.1038/ng.3917

18. Ramasamy K, Narayan SK, Shewade DG, Chandrasekaran A. Influence of CYP2C9 genetic polymorphism and undernourishment on plasma-free phenytoin concentrations in epileptic patients. Ther Drug Monit. 2010;32(6):762766. doi:10.1097/FTD.0b013e3181fa97cc

19. Tang C, Shou M, Rushmore TH, et al. In-vitro metabolism of celecoxib,
a cyclooxygenase-2 inhibitor, by allelic variant forms of human liver microsomal cytochrome P450 2C9: correlation with CYP2C9 genotype and in-vivo pharmacokinetics. Pharmacogenetics. 2001;11(3):223235. doi:10.1097/00008571-200104000-00006

20. Zhou K, Donnelly L, Burch L, et al. Loss-of-function CYP2C9 variants improve therapeutic response to sulfonylureas in type 2 diabetes: a Go-DARTS study. Clin Pharmacol Ther. 2010;87(1):5256.

21. Lee CR, Goldstein JA, Pieper JA. Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data. Pharmacogenetics. 2002;12(3):251263. doi:10.1097/00008571-200204000-00010

22. Yasar U, Tybring G, Hidestrand M, et al. Role of CYP2C9 polymorphism in losartan oxidation. Drug Metab Dispos. 2001;29(7):10511056.

23. Thorn CF, Klein TE, Altman RB. PharmGKB: the pharmacogenomics knowledge base. Methods Mol Biol. 2013;1015:311320.

24. Williams PA, Cosme J, Ward A, Angove HC, MatakVinkovic D, Jhoti H. Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature. 2003;424(6947):464468. doi:10.1038/nature01862

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[Full text] CYP2C9 Variations and Their Pharmacogenetic Implications Among Diverse | PGPM - Dove Medical Press

A local doctor explains what's in the COVID-19 vaccine and how it works.

MEMPHIS, Tenn Concerns about the COVID-19 vaccine remain.

It's the first vaccine without a living virus, but some are concerned over what's in the COVID-19 vaccine.

"This vaccine is the result of, really, some genetic engineering. They are able to sequence the virus, decode it and find the genetic code for just a part of the virus, specifically the spike that is located on the outside of the virus," said Dr. Bruce Randolph of the Shelby County Health Department.

He says that's the part of the virus that attaches to the human cell.

Worried the vaccine arrived too soon?

COVID-19 may have entered American consciousness about 9 months ago, but scientists have studied different forms of the Coronavirus for years.

The variations go back some 10-thousand years.

Researchers are also keeping an eye on a new variant called B-1-17 found in a few states, but not yet in Tennessee.

"This particular virus is five times more easier to transmit than the Coronavirus we are dealing with at the current time," said Randolph.

For example, Randolph explains if COVID-19 takes 100 droplets for infection, this new strain might only take 10.

With 72-thousand COVID cases just reported in Shelby County a new strain would cause great concern.

"If this variant strain hit Shelby County those number could be as much as 5 times higher," said Randolph.

Researchers believe the current vaccine will provide immunity for that new strain.

the Memphis-Shelby County task force are urging everybody to get educated, talk to your doctor, get vaccinated and keep up with your card.

"You would be able to go wherever and present your card and say I need my second dose and the provider would know exactly when you last received, if it's indeed time for you to receive your second dose and what vaccine you received because you shouldn't mix them."

Read the original post:
What the emerging new strain of the Coronavirus means for the vaccine - WATN - Local 24

Takeaways

Scientists have made progress growing human liver in the lab.

The challenge has been to direct stems cells to grow into a mature, functioning adult organ.

This study shows that stem cells can be programmed, using genetic engineering, to grow from immature cells into mature tissue.

When a tiny lab-grown liver was transplanted into mice with liver disease, it extended the lives of the sick animals.

Imagine if researchers could program stem cells, which have the potential to grow into all cell types in the body, so that they could generate an entire human organ. This would allow scientists to manufacture tissues for testing drugs and reduce the demand for transplant organs by having new ones grown directly from a patients cells.

Im a researcher working in this new field called synthetic biology focused on creating new biological parts and redesigning existing biological systems. In a new paper, my colleagues and I showed progress in one of the key challenges with lab-grown organs figuring out the genes necessary to produce the variety of mature cells needed to construct a functioning liver.

Induced pluripotent stem cells, a subgroup of stem cells, are capable of producing cells that can build entire organs in the human body. But they can do this job only if they receive the right quantity of growth signals at the right time from their environment. If this happens, they eventually give rise to different cell types that can assemble and mature in the form of human organs and tissues.

The tissues researchers generate from pluripotent stem cells can provide a unique source for personalized medicine from transplantation to novel drug discovery.

But unfortunately, synthetic tissues from stem cells are not always suitable for transplant or drug testing because they contain unwanted cells from other tissues, or lack the tissue maturity and a complete network of blood vessels necessary for bringing oxygen and nutrients needed to nurture an organ. That is why having a framework to assess whether these lab-grown cells and tissues are doing their job, and how to make them more like human organs, is critical.

Inspired by this challenge, I was determined to establish a synthetic biology method to read and write, or program, tissue development. I am trying to do this using the genetic language of stem cells, similar to what is used by nature to form human organs.

I am a researcher specializing in synthetic biology and biological engineering at the Pittsburgh Liver Research Center and McGowan Institute for Regenerative Medicine, where the goals are to use engineering approaches to analyze and build novel biological systems and solve human health problems. My lab combines synthetic biology and regenerative medicine in a new field that strives to replace, regrow or repair diseased organs or tissues.

I chose to focus on growing new human livers because this organ is vital for controlling most levels of chemicals like proteins or sugar in the blood. The liver also breaks down harmful chemicals and metabolizes many drugs in our body. But the liver tissue is also vulnerable and can be damaged and destroyed by many diseases, such as hepatitis or fatty liver disease. There is a shortage of donor organs, which limits liver transplantation.

To make synthetic organs and tissues, scientists need to be able to control stem cells so that they can form into different types of cells, such as liver cells and blood vessel cells. The goal is to mature these stem cells into miniorgans, or organoids, containing blood vessels and the correct adult cell types that would be found in a natural organ.

One way to orchestrate maturation of synthetic tissues is to determine the list of genes needed to induce a group of stem cells to grow, mature and evolve into a complete and functioning organ. To derive this list I worked with Patrick Cahan and Samira Kiani to first use computational analysis to identify genes involved in transforming a group of stem cells into a mature functioning liver. Then our team led by two of my students Jeremy Velazquez and Ryan LeGraw used genetic engineering to alter specific genes we had identified and used them to help build and mature human liver tissues from stem cells.

The tissue is grown from a layer of genetically engineered stem cells in a petri dish. The function of genetic programs together with nutrients is to orchestrate formation of liver organoids over the course of 15 to 17 days.

I and my colleagues first compared the active genes in fetal liver organoids we had grown in the lab with those in adult human livers using a computational analysis to get a list of genes needed for driving fetal liver organoids to mature into adult organs.

We then used genetic engineering to tweak genes and the resulting proteins that the stem cells needed to mature further toward an adult liver. In the course of about 17 days we generated tiny several millimeters in width but more mature liver tissues with a range of cells typically found in livers in the third trimester of human pregnancies.

Like a mature human liver, these synthetic livers were able to store, synthesize and metabolize nutrients. Though our lab-grown livers were small, we are hopeful that we can scale them up in the future. While they share many similar features with adult livers, they arent perfect and our team still has work to do. For example, we still need to improve the capacity of the liver tissue to metabolize a variety of drugs. We also need to make it safer and more efficacious for eventual application in humans.

[Deep knowledge, daily. Sign up for The Conversations newsletter.]

Our study demonstrates the ability of these lab livers to mature and develop a functional network of blood vessels in just two and a half weeks. We believe this approach can pave the path for the manufacture of other organs with vasculature via genetic programming.

The liver organoids provide several key features of an adult human liver such as production of key blood proteins and regulation of bile a chemical important for digestion of food.

When we implanted the lab-grown liver tissues into mice suffering from liver disease, it increased the life span. We named our organoids designer organoids, as they are generated via a genetic design.

Mo Ebrahimkhani, Associate Professor of Pathology and Bioengineering, University of Pittsburgh

This article is republished from The Conversation under a Creative Commons license. Read the original article.

then let us make a small request. The COVID crisis has slashed advertising rates, and we need your help. Like you, we here at Raw Story believe in the power of progressive journalism. Raw Story readers power David Cay Johnstons DCReport, which we've expanded to keep watch in Washington. Weve exposed billionaire tax evasion and uncovered White House efforts to poison our water. Weve revealed financial scams that prey on veterans, and legal efforts to harm workers exploited by abusive bosses. And unlike other news outlets, weve decided to make our original content free. But we need your support to do what we do.

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then let us make a small request. The COVID crisis has slashed advertising rates, and we need your help. Like you, we believe in the power of progressive journalism and were investing in investigative reporting as other publications give it the ax. Raw Story readers power David Cay Johnstons DCReport, which we've expanded to keep watch in Washington. Weve exposed billionaire tax evasion and uncovered White House efforts to poison our water. Weve revealed financial scams t
hat prey on veterans, and efforts to harm workers exploited by abusive bosses. We need your support to do what we do.

Raw Story is independent. You wont find mainstream media bias here. Every reader contribution, whatever the amount, makes a tremendous difference. Invest with us in the future. Make a one-time contribution to Raw Story Investigates, or click here to become a subscriber. Thank you.

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Genetic engineering transformed stem cells into working ...

Every cell in your body has around 3 billion base pairs of DNA code inside it. Just a few small errors in this code could leave someone with a debilitating illness. Molecular biologist Eric Olsen has described it as equivalent to misspelling one word in a stack of one thousand bibles, and this tiny typo could put a child in a wheelchair for life.

Researchers have already identified DNA errors as the cause of nearly 7,000 diseases. Thankfully, the growing world of genome editing could be the "spell-checker" needed to detect and eventually fix these problems.

Genome editing is often equated with designer babies and CRISPR/Cas9. However, the world of genome editing is far more diverse and complex and goes well beyond just CRISPR, which is only the latest in a long line of editing "tools". Genome engineering is a type of genetic engineering in which DNA is inserted, deleted, modified, or replaced in the genome of a living organism.

It is an incredibly powerful tool with tremendous potential in the field of medicine. In its simplest form, it is a way of making specific changes to the DNA of an organism. It's similar to editing the code in a piece of computer software.

There is a reason why there is a lot of hype around gene editing, and you should be excited too. Genome editing could potentially be used to treat major degenerative diseases and fix simple genetic conditions like muscular dystrophy. It may one day soon be used to grow new human organs in pigs, combat the constant demand for organ transplants, and potentially turn human reproduction on its head, yes, we're talking about using it to engineer entire populations.

We are still a ways away from the movie Gattaca, or Aldous Huxley's Brave New World. Nonetheless, real-world gene engineering poses some very interesting ethical questions. Today we are going to look at the history of genome editing, new methods like CRISPR, as well as alternatives, and look at some of the ethical questions currently plaguing this medical tool.

Okay, to review, genome editing or gene editing is a relatively new method that lets scientists change the DNA from bacteria to animals. These "edits" could potentially lead to changes in physical traits like eye color, or, more importantly, to cure certain diseases. Genome editing has already been used in agriculture to modify crops to improve their yields and increase their resistance to disease and drought.

There are many different methods and technologies used to edit DNA. Nonetheless, most of these technologies generally act like the "cutting" and "pasting" functions on your computer, allowing scientists to alter the DNA at a specific spot in an organisms' genome. Though much of the hype around gene editing centers around its power to engineer humans, the main application of genome editing so far has been in plants and some animals in lab settings.

Once it was realized in the 1940s that DNA was responsible for heredity, and once the structure of the DNA molecule was elucidated in the 1950s,researchers realized that errors in this genetic code were responsible for many diseases and inherited conditions.

The question that followed was an obvious one. Could these errors be corrected? This question led to the emergence of genetic engineering in the 1970s, where new genetic code was introduced into organisms' DNA. However, this technology was not initially capable of inserting the new material in a highly targeted way.

One early example of targeting genes to certain sites within a genome of an organism usedhomologous recombination. This method involves the construction of a sort of template that matched the targeted genome sequence, and relied on the normal cell processes to insert this template at the correct location. The method was successfully used to introduce genetic modifications in mice using embryonic stem cells.

Another early method used conditional targeting using enzymes calledsite-specific recombinases(SSR). These techniques were able toknock out or switch on genes only in certain cells and ultimately allowed researchers to induce recombination under certain conditions, allowing genes to be knocked out or expressed at particular times or at particular stages of development.

The key to genome editing is creating a double-stranded break(DSB) in the genome at a specific point and removing the erroneous part of the genetic code. Enzymes are then used to repair the break, rejoining the ends of the DNA or to insert the missing correct sequences in the correct location. However, while certainenzymes are effective at cutting DNA, they generally cut at several multiple sites - potentially removing DNA that researchers do not want removed. To overcome this challenge, several types of nucleases (enzymes) have been created. These are called Zinc finger nucleases (ZFNs), transcription-activator like effector nucleases (TALEN), meganucleases, and the clustered regularly interspaced short palindromic repeats (CRISPR/Cas9).

Meganucleases werediscovered in the late 1980s, they canrecognize and cut DNA sequences of between 14 and 40 base pairs. However, it can be difficult to engineer nucleases that will cut the DNA at the exact site needed. Recently, a library of sorts has been created that has allowed scientists to more easily create meganucleases that will cut in specific locations. For example, there are now meganucleases able to remove mutations to the human XPC gene which causeXeroderma pigmentosum, a disorder that predisposes the patients to skin cancer and burns when exposed to UV light.

In the 1990s, scientists used zinc-finger nucleases to improve existing gene-editing techniques. These synthetic proteins are used for gene targeting and are composed of DNA-cutting endonuclease domains fused to zinc finger domains engineered to bind a specific DNA sequence. They can be used to add or delete cut sites in the genomes of cells. Though this method has been dramatically improved, the success rate is still only about 10 percent. Even more so, this gene-editing method is costly and time-consuming to design.

Transcription activator-like effector nucleases (TALEN) share some similarities to Zinc-finger nucleases. Developed in 2009, TALENs are engineered from proteins found in nature and are capable of binding to specific DNA sequences. And while their effectiveness and efficiency parallel ZFN, they are far easier to engineer.

While ZFN and TALEN do offer effective genome editing, one drawback is that they are both time-consuming and expensive to develop. And, the process of engineering proteins is prone to error. CRISPR is so revolutionary in gene editing realms because it offers scientists a faster and simpler way to edit the genome, "with little assembly required." CRISPR/Cas9 was already on the radar of researchers in the 1990s, but its full potential was not realized until recent years.

CRISPR/Cas9 is a powerful new gene-editing technology developed separately in around 2012 by scientists Feng Zhang, Jennifer Doudna, and Emmanuelle Charpentier.

CRISPR can recognize specific genome sequences and cut them often utilizing the Cas9 protein.

CRISPR technology is based on a defense mechanism that bacteria use to fight viruses. Viruses attack cells by using the cells' own machinery to create replicas of themselves. Eventually, the cell bursts and the virus copies are released into the organism to infect new cells. However, bacteria have evolved a way to fight back by cutting up the virus' DNA. If a bacteria survives a virus attack, they copy pieces of that virus' DNA and incorporate these into its own genomes. These copies are used like mugshots to allow the bacteria to identify harmful viruses.

To keep track of this collection of "mugshots" and to keep them separate from the bacteria's own DNA, repetitive sequences of molecules are placed around each sequence that was taken from a virus. When a bacteria comes up against a virus with a sequence in its collection, the bacteria sends an enzyme to cut ap
art and destroy anything that matches the genetic mugshot. CRISPR allows scientists to use a similar approach, often using the protein Cas9 to cut and replace specific gene sequences.

The CRISPR technique allows scientists to quickly and efficiently alter almost any gene in any plant or animal at a low cost. Researchers already have used the technique to correct genetic diseases in animals, grow crops more resilient to a certain climate, alter pig organs for easier human transplantation, sterilize mosquitos for disease prevention, and add muscle mass to beagles.

Scientists are also able to use CRISPR to create short RNA templates that match a targeted sequence in the genome, making the process of editing far easier, efficient, cheaper, and quicker. CRISPR is currently being used to develop treatments for HIV, Duchenne muscular dystrophy, some types of blindness, and Lyme disease just to name a few.

"CRISPR is incredibly powerful. It has already brought a revolution to the day-to-day life in most laboratories. I am very hopeful that over the next decade gene editing will transition from being a primarily research tool to something that enables new treatments in the clinic,"saidNeville Sanjana, of the New York Genome Center and an assistant professor of biology, neuroscience, and physiology at New York University.

Gene-editingtools like CRISPRcould give scientists the keys to the DNA kingdom, allowing us to find "molecular mistakes" and remove them. According to Nicola Patron, a molecular and synthetic biologist at the Earlham Institute in the UK, "We are getting to a point where we can investigate different combinations of genes, control when, where, and how much they are expressed, and investigate the roles of individual bases of DNA. Understanding what DNA sequences do is what enables us to solve problems in every field of biology from curing human diseases, to growing enough healthy food, to discovering and making new medicines, to understand why some species are going extinct."

Researchers could one day remove malaria from mosquitoes. Researchers have already created mosquitoes that are resistant to malaria by deleting a specific segment of mosquitoes' DNA. Neurodegenerative diseases like Alzheimer's and Parkinson's could potentially become a thing of the past. Scientists are already working on CRISPR-based platforms to identify the genes controlling the cellular processes that lead to neurodegenerative diseases. In 2017, researchers used CRISPR to shut down the HIV virus' ability to replicate, eliminating the HIV virus from infected cells.

In 2016, a lung cancer patient in China became the first human to receive an injection of cells that had been modified using CRISPR. Researchers used CRISPR to disable a gene used by the cancer cells to divide and multiply. Without the gene, researchers hope the cancer cells will not multiply.

From agriculture to pharmaceuticals, gene editing could one day help us build a better world.

Yes and no. Designer babies seem to lead the conversation when discussing CRISPR. Ethical questions like, "Is it okay to use gene therapy on an embryo when it is impossible to get permission from the embryo for treatment?" or "What if gene therapies are too expensive and only wealthy people can access and afford them?" lay at the core of most people's concerns.

What if people use these tools to improve a child's athletic ability or height rather than use it for treating diseases?

Would this lead to genetic discrimination? Though researchers are still navigating the arguments for and against, gene editing in humans has already begun.

The US, China, andthe UKhave approved gene editing in humans for research purposes only.

Even popular gene-editing tools like CRISPR are still not perfect. In some cases, the gene-editing tools make cuts in the wrong places, and researchers are still not 100% sure how that will affect people. Properly addressing the ethical concerns and ensuring gene editing safety are still two massive mountains that scientists need to climb before we see mainstream genome treatments.

In her book, A Crack in Creation: The New Power to Control Evolution,Jennifer A. Doudas paints us a picture of a gene-edited world, stating, "Tomatoes that can sit in the pantry slowly ripening for months without rotting. Plants that can weather climate change better. Mosquitoes that are unable to transmit malaria. Ultra-muscular dogs that make fearsome partners for police and soldiers. Cows that no longer grow horns."

She adds: "These organisms might sound far-fetched, but in fact, they already exist, thanks to gene editing. And they're only the beginning. As I write this, the world around us is being revolutionized by CRISPR, whether we're ready for it or not."

It does not sound too bad, right? What is your opinion on gene-editing? How will it change the world?

See the article here:
Everything You Need to Know About Genome Editing - Interesting Engineering

The lab of KrisSaha at the University of WisconsinMadison has developed an innovative combination of gene-editing tools and computational simulations that can be used to develop new strategies for editing genes associated with genetic disorders.

In proof-of-concept experiments, the labs researchers efficiently corrected multiple mutations responsible for a rare metabolic disorder, known as Pompe disease, in cells containing the disease-causing errors. They also used computer simulations to design the ideal gene-editing approach for treating human patients, a boon for rare disorders like Pompe disease that lack useful animal models.

Their promising platform advances the CRISPR genome-editing field and could lead to effective treatments for many diseases, not just Pompe disease.

The exact mutations seen in the Pompe patients are not in an existing animal model, so we cannot do all of the preclinical studies that we would like to do in order to evaluate the safety and efficacy of different genome editing strategies, says Saha, a professor of biomedical engineering at UWMadisons Wisconsin Institute for Discovery. We need a way to think about how we go from patient material to a therapy without having to build an animal model, a process that takes months to years and hundreds of thousands of dollars.

The lab of Kris Saha (standing) has developed an innovative combination of gene-editing tools and computational simulations that can be used to develop new strategies for editing genes associated with genetic disorders. Photo: Stephanie Precourt

Sahas team published its findings Dec. 8 in the journal Nature Communications.

In the first few months of life, an infant with Pompe disease becomes weaker and weaker as glycogen builds up in their muscles, their cells unable to break the complex sugar down. Multiple mutations in a gene calledGAAprevent their cells from correctly producing the proteins needed to make lysosomes, which turn glycogen into glucose, the fuel that powers cells. Left untreated, most patients with Pompe die within a year.

Developing effective therapies for such diseases can be difficult for a number of reasons. First, diseases like Pompe have no animal models in which to test treatments, a typical step in therapy development. And diseases like Pompe and many other inherited diseases are autosomal recessive, which means that mutations are present on both copies of a chromosome. Two sets of mutations require two successful gene-repair events for maximum effect. Further complicating the matter is the fact that many diseases are polygenic, resulting from mutations in two or more genes or multiple mutations spread across a single gene, as is the case for Pompe disease.

The Saha labs new approach uses precise gene-editing tools to edit both faulty alleles simultaneously within individual cells to restore function. In its new report, the research team used induced pluripotent stem cells derived from Pompe patients to reproduce the exactGAAmutations that cause the disease and to approximate the resulting tissue pathology.

To fix these Pompe mutations, the lab turned to a specially designed, ultra-precise genome-editing system described in aprevious studyled by Jared Carlson-Stevermer, who was at the time a graduate student in Sahas group. That report established an up to 18-fold increase in precision of gene edits by combining a DNA repair template with the cutting machinery of CRISPR in one particle.

In the current study, the researchers used the method to fix two mutations at once in Pompe-derived cells. By doing so, the researchers improved cell function dramatically, bringing lysosome protein production up to the level of healthy cells without any major adverse effects, which sometimes emerge from gene editing.

The research advances the CRISPR genome-editing field and could lead to effective treatments for many diseases.

But treating cells in the laboratory, while providing crucial insight, is not the same as creating a therapy for patients. A critical step in developing treatments usually involves testing on animal models to evaluate efficacy and safety, a major obstacle for Pompe disease and other genetic conditions that lack viable animal models.

To determine the best therapeutic strategy for polygenic diseases evaluating different doses, delivery mechanisms and timing, risks and other factors the research team instead built a computational model that allows it to predict the outcomes of various conditions.

This allows us to survey a wider scope of many different gene therapies during the design of a strategy, says coauthor Amritava Das, a postdoctoral associate at the Morgridge Institute for Research. The computational approach is critical when you dont have an animal model that resembles the human disease.

After pumping close to a million simulation conditions through the computational model, Das, Carlson-Stevermer and Saha have gained key insights about the delivery of gene editors into the livers of human infants with Pompe disease without having to subject a single patient to experimental treatments. And those insights establish that the multiple-correction genome-editing approach tested in stem cells may be an effective treatment for Pompe and other polygenic recessive disorders.

The computational model, which can be easily adapted for other polygenic conditions, is a big step for the development of therapies for diseases like Pompe and lays the groundwork for a bridge from laboratory studies to the clinic. And as more measurements are added to the model, it will gain more predictive power.

Its a very broad, adaptable platform, Das says about the combined stem cell model and computational tool, and a very different way of thinking about gene therapy.

This work was supported by the National Science Foundation (CBET-1350178, CBET-1645123), the National Institutes of Health (1R35GM119644-01), the Environmental Protection Agency (EPA-G2013 STAR-L1), the University of Wisconsin Carbone Cancer Center (P30 CA014520), the Wisconsin Alumni Research Foundation, and the Wisconsin Institute for Discovery.

Read the rest here:
Multiple gene edits and computer simulations could help treat rare genetic diseases - University of Wisconsin-Madison

A new study associates a gene that facilitates neuron communication in the nervous system with memory loss.

A recent study1 led by The Jackson Laboratory and University of Maine has discovered that the gene Dlgap2 is associated with Alzheimer disease, dementia, and cognitive decline. Researchers found post-mortem human brain tissues of individuals experiencing poorer cognitive health and faster cognitive decline had low levels of Dlgap2.

The reason why this is so important is because a lot of research around cognitive aging and Alzheimers has been hyper-focused on well-known risk genes like APOE and brain pathologies, Catherine Kaczorowski, associate professor and Evnin family chair in Alzheimer disease research at The Jackson Laboratory (JAX), and adjunct professor with the University of Maine Graduate School of Biomedical Science and Engineering (GSBSE), said to the press. We wanted to give ourselves the option of looking at new things people keep ignoring because they've never heard about a gene before.2

Located in the synapses of neurons, Dlgap2 anchors critical receptors for signals between learning and memory neurons. The research team examined the memory and brain tissue from a large group of genetically diverse mice, relying on diversity outbred mice. The population came from 8 parents created by JAX, as they thought a diversified group would better reflect genetic diversity in humans. About 437 mice, eacheither 6, 12, or 18 months old were used.

Its great because you can harness the best parts of a mouse study and human society, Andrew Ouellette, a PhD student at JAX and a GSBSE NIH T32 predoctoral awardee, said to the press. Historically, research has been done with inbred mice with similar genetic makeups; same, similar genetic models. But clinically, humans don't work like that because they're not genetically identical.2

Quantitative trait loci mapping was performed on the mouse population. Study of entire genome sequences allowed for identification of the genes responsible for varying cognitive function and where they occurred. Researchers pinpointed the connection between Dlgap2 and memory decline in mice, and were then able to evaluate its significance to humans.

They found Dlgap2 is associated with the degree of memory loss in mice and risk for Alzheimer dementia in humans. Further research will be needed to determine how the gene influences dementia and brain functioning.

References

1. Ouellette AR, Neuner SM, Dumitrescu L, Hadad N, et al. Cross-species analyses identify Dlgap2 as a regulator of age-related cognitive decline and alzheimers dementia. Cell Reports. 2020;32(9):108091.

2. University of Maine. New connection between Alzheimer's dementia and Dlgap2. News release. ScienceDaily. November 23, 2020. https://www.sciencedaily.com/releases/2020/11/201123161040.htm

Read the original here:
Dlgap2: The Gene Associated With Memory Loss - Psychiatric Times

Researchers at Washington University School of Medicine in St. Louis have identified a molecule that protects mice from brain infections caused by Venezuelan equine encephalitis virus (VEEV), a mosquito-borne virus notorious for causing fast-spreading, deadly outbreaks in Mexico, Central America and northern South America. As the climate changes, the virus is likely to expand its range and threaten more countries in the Americas, including the U.S.

Public health officials have struggled to contain such outbreaks in the absence of effective drugs and vaccines. As a potential drug, the molecule -- described in a paper published Nov. 18 in the journal Nature -- could serve as a much needed tool to control the deadly virus.

"This virus can infect many species of wild mammals, and every few years it jumps from animals to humans via mosquitoes and causes thousands of infections and many deaths," said senior author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine and a professor of molecular microbiology, and of pathology and immunology. "There's concern that with global warming and population growth, we'll get more outbreaks."

Once injected under the skin by mosquitoes, the virus homes in on neurons. People start experiencing symptoms such as headache, muscle pain, fatigue, vomiting, nausea, diarrhea, sore throat and fever within a week. In the most serious cases, the virus gets past the blood-brain barrier, causing encephalitis -- brain inflammation that can be fatal in up to a quarter of patients.

To find the potential drug, Diamond and colleagues -- including first authors Hongming Ma, PhD, an instructor in medicine, and Arthur S. Kim, PhD, a postdoctoral researcher -- began by searching for the protein "handle" on the surface of animal cells that the virus attaches to and uses to get inside cells. A drug that stops the virus from grabbing that handle, the scientists reasoned, could stymie infection and prevent disease.

But first they had to make a form of the virus they could work easily with. During the Cold War, the U.S. and the Soviet Union attempted to weaponize the virus, and it is still classified as a select agent, meaning only certain high-security labs are allowed to work with it. So instead, the researchers and their colleagues took Sindbis virus, a related virus that causes mild fever and rash, and swapped out some of its genes for some from VEEV. The resulting hybrid virus, called Sindbis-VEEV, infects cells like authentic VEEV but is unable to cause severe disease.

Using a genetic engineering technique known as genome-wide CRISPR screening, the researchers deleted genes in mouse neuronal cells until they found one -- called Ldlrad3 -- whose absence kept Sindbis-VEEV from infecting cells. The missing gene codes for a little-studied surface protein.

Further experiments verified the importance of Ldlrad3. Adding the gene back to neuronal cells restored the virus's ability to infect cells. The human LDLRAD3 gene is almost identical to its mouse equivalent, and knocking out the human gene also reduced infection in multiple cell lines. When the researchers added Ldlrad3 to a different cell type that is normally resistant to infection, the virus was able to infect the cell. Co-author William Klimstra, PhD, at the University of Pittsburgh, separately replicated the findings using authentic, highly virulent VEEV.

Ldlrad3 doesn't appear to be the only way the virus gets inside cells, since a small amount of virus is able to infect cells lacking the protein. But it is clearly the primary way in. Since Ldlrad3 is naturally on our cells and can't be removed, the scientists decided to create a decoy handle using a piece of the Ldlrad3 protein. Any virus particles that mistakenly latch onto the decoy handle would fail to infect cells and instead would get destroyed by the immune system.

To test their decoy in a living animal, the researchers injected mice with authentic virulent VEEV in two different ways: under the skin to mimic a mosquito bite, or directly into the brain. They gave the mice the decoy handle or a placebo molecule for comparison, either six hours before or 24 hours after infection. In all experiments, all of the mice that received the placebo died within a week. In most cases, all of the mice that received the decoy molecule survived, although in the most stringent experiment -- in which the virus was injected into the brain -- two of the 10 mice died despite receiving the decoy.

"In an outbreak situation, you may be able to use a drug like this as a countermeasure to prevent transmission and further spread," Diamond said.

A major advantage to an antiviral drug based on a human -- rather than a viral -- protein is that it is unlikely the virus could evolve resistance to it. Any mutation that enables the virus to avoid the decoy probably would make it unable to attach to cells, too, the researchers said.

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Lethal brain infections in mice thwarted by decoy molecule - Science Codex