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Gene therapies deliver healthy genetic material to patients cells to replace a mutated, disease-causing variant. Dyno Therapeutics aims to create better delivery vehicles for those genes by using machine-learning tools to engineer new types of harmless viruses that are more effective and simpler to manufacture.

The Cambridge, MA-based biotech emerged from stealth Monday having signed deals with two drug makers who want to apply its technology to their gene therapy effortsagreements its founders say are lucrative enough to fund the company for years to come. Dyno spun out of George Churchs lab at Harvard Medical School in late 2018 with $9 million in seed funding from Polaris Partners and CRV.

Now Dyno has signed collaboration agreements with Novartis (NYSE: NVS) and Sarepta Therapeutics (NASDAQ: SRPT) to design superior versions of the adeno-associated viruses, or AAVs, commonly used in gene therapies, and the company says the deals may preclude it from needing to raise outside funds again. Thats a rarity for a biotech that is already considering advancing its own product candidates in addition to striking R&D arrangements with other biotechs and pharmaceutical companies.

The first gene therapy in the US was approved in 2017. Finding better AAVs in which to insert genetic material has proven challenging because tweaking the complex protein shells to improve one property, such as targeted delivery, can impede others, such as their ability to evade the immune system.

With small molecules and antibodies, the drug is the small molecule or the antibody, and sometimes youll require a delivery system but thats not the important part, Polaris partner Alan Crane, one of Dynos founders, said in an interview. Its almost flipped in gene therapy, because everyone knows what gene to deliver, generally, for a particular disease, but they dont know how to deliver it, and we really need these better vectors.

Dyno will work with Novartis to use its CapsidMap platform to design superior AAV vectors for gene therapies for eye diseases; Sareptas area of interest is muscle disease.

Under the terms of the deals, the larger companies will be responsible for taking any gene therapy product candidates created within the collaborations through preclinical and clinical testing and commercialization. In the Novartis agreement, Dyno gets an undisclosed amount of money up front plus research funding and license fees. If any products advance, it will be eligible for payments tied to clinical, regulatory, and sales milestones, plus royalties on sales.

In the Sarepta agreement, during the research phase of the collaboration, Dyno will be eligible for more than $40 million in payments. If candidates are developed, it will be eligible for additional payments tied to development milestones, plus royalties. The company wouldnt disclose additional financial details, but said if everything goes according to plan, the deals it has struck to date could collectively bring the startup more than $2 billion.

CEO Eric Kelsic said that when he joined Churchs lab, he aimed to use his experimental and computational biology background to combine the latest technologies in high-throughput biology, advanced machine learning, and protein engineering. He was exposed to gene therapy through Churchs work with the gene editing technology CRISPR-Cas9, one of the tools being deployed to address genetic diseases.

It just seemed like the perfect application of the technologies we had been working on, which are certainly going to transform all of protein engineering, Kelsic said in an interview.

The company takes available data, plus more it generates itself using high-throughput measurement technologies, and uses it to build machine-learning models that suss out the most optimal synthetic capsids. Using machine learning allows Dyno to take into account a number of important propertiesdelivery, immunity, packaging size, and manufacturing, for examplewhile weighting those most important to the particular disease indication. Thats compared to todays efforts, which generally can only tweak one property at a time.

Its been the case in the past that when you only select for one property, for example the efficiency of delivery, that might be improved, but the manufacturability might actually get more challenging, Kelsic said. Thats a tradeoff which has really limited engineering efforts in this space, but now we can overcome that using our platform, optimizing for both the efficiency and the manufacturability and so on, across all the different properties that are important.

Machine-learning tools also allow each experiment to build upon the findings of previous iterations.

When Crane and Kelsic first met, in June 2018, the scientist presented the investor with a spreadsheet of companies that were interested in what the startup had developed. That was before Dyno had published any of its results.

Before joining Polaris in 2002, Crane headed corporate development at Millennium Pharmaceuticals. (Takeda Pharmaceutical (NYSE: TAK) acquired Millennium in 2008 for $8.8 billion). Since joining the VC firm in 2002, Crane has been founder, chairman, or CEO of seven of the companies it has started.

We and a lot of folks in the VC world have been looking at AI applications to healthcare, and increasingly to life sciences and biology, but this was by far the best application to biology that I have ever seen, Crane said. Ive seen a lot of business development, and Ive never seen such robust interest in a young company platform.

Crane says Dyno is currently in talks with other companies that will likely lead to one or two more partnerships like those it has struck with Novartis and Sarepta. The company says it wont allow any company to use its tech to explore a certain disease area exclusively so that it can potentially be used across the industry. In addition to eye and muscle diseases, company is also looking at how to design better vectors for disorders of the central nervous system and the liver.

Along with Kelsic, Church, and Crane, Dynos co-founders are Sam Sinai, its lead machine learning scientist, Adrian Veres, and Tomas Bjorklund.

Sarah de Crescenzo is an Xconomy editor based in San Diego. You can reach her at sdecrescenzo@xconomy.com.

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Dyno Debuts With Plan, Partnerships For Better Gene Therapy Vectors - Xconomy

The Research Brief is a short take about interesting academic work.

When some people become infected with the coronavirus, they only develop mild or undetectable cases of COVID-19. Others suffer severe symptoms, fighting to breathe on a ventilator for weeks, if they survive at all.

Despite a concerted global scientific effort, doctors still lack a clear picture of why this is.

Could genetic differences explain the differences we see in symptoms and severity of COVID-19?

To test this, we used computer models to analyze known genetic variation within the human immune system. The results of our modeling suggest that there are in fact differences in peoples DNA that could influence their ability to respond to a SARS-CoV-2 infection.

When a virus infects human cells, the body reacts by turning on what are essentially anti-virus alarm systems. These alarms identify viral invaders and tell the immune system to send cytotoxic T cells a type of white blood cell to destroy the infected cells and hopefully slow the infection.

But not all alarm systems are created equal. People have different versions of the same genes called alleles and some of these alleles are more sensitive to certain viruses or pathogens than others.

To test whether different alleles of this alarm system could explain some of the range in immune responses to SARS-CoV-2, we first retrieved a list of all the proteins that make up the coronavirus from an online database.

We then took that list and used existing computer algorithms to predict how well different versions of the anti-viral alarm system detected these coronavirus proteins.

The part of the alarm system that we tested is called the human leukocyte antigen system, or HLA. Each person has multiple alleles of the genes that make up their HLA type. Each allele codes for a different HLA protein. These proteins are the sensors of the alarm system and find intruders by binding to various peptides chains of amino acids that make up parts of the coronavirus that are foreign to the body.

Once an HLA protein binds to a virus or piece of a virus, it transports the intruder to the cell surface. This marks the cell as infected and from there the immune system will kill the cell.

In general, the more peptides of a virus that a persons HLAs can detect, the stronger the immune response. Think of it like a more sensitive sensor of the alarm system.

The results of our modeling predict that some HLA types bind to a large number of the SARS-CoV-2 peptides while others bind to very few. That is to say, some sensors may be better tailored to SARS-CoV-2 than others. If true, the specific HLA alleles a person has would likely be a factor in how effective their immune response is to COVID-19.

Because our study only used a computer model to make these predictions, we decided to test the results using clinical information from the 2002-2004 SARS outbreak.

We found similarities in how effective alleles were at identifying SARS and SARS-CoV-2. If an HLA allele appeared to be bad at recognizing SARS-CoV-2, it was also bad at recognizing SARS. Our analysis predicted that one allele, called B46:01, is particularly bad with regards to both SARS-CoV-2 and SARS-CoV. Sure enough, previous studies showed that people with this allele tended to have more severe SARS infections and higher viral loads than people with other versions of the HLA gene.

Based on our study, we think variation in HLA genes is part of the explanation for the huge differences in infection severity in many COVID-19 patients. These differences in the HLA genes are probably not the only genetic factor that affects severity of COVID-19, but they may be a significant piece of the puzzle. It is important to further study how HLA types can clinically affect COVID-19 severity and to test these predictions using real cases. Understanding how variation in HLA types may affect the clinical course of COVID-19 could help identify individuals at higher risk from the disease.

To the best of our knowledge, this is the first study to evaluate the relationship between viral proteins across a wide range of HLA alleles. Currently, we know very little about the relationship between many other viruses and HLA type. In theory, we could repeat this analysis to better understand the genetic risks of many viruses that currently or could potentially infect humans.

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Your genes could determine whether the coronavirus puts you in the hospital and we're starting to unravel which ones matter - The Conversation US

As if 2020 could get any worse, in addition to the suspicious recent rash of Russian doctors falling out of windows there is now news of another potential disaster heading west from Asia: murder hornets, also known as Vespa mandarinia or the Asian giant hornet.

These insects, cartoonishly festooned in orange and black, live up to their intensely predatory notoriety. Growing to an astounding 5 centimeters in length, with a wingspan of 7.5 cm, they are capable of flying more than 30 kilometers per hour. The females also brandish a quarter-inch reusable stinger loaded with a lethal venomous mix of flesh-eating chemicals and a neurotoxin that can lead to cardiac arrest and anaphylactic shock. The very aggressive hornet reportedly kills 30-50 people every year in Japan.

Recently, multiple distinct colonies have emerged in North Americas Pacific Northwest, in both Canada and the U.S. Infamous for decimating Asian honeybee hives by ferociously decapitating the entire colony and feeding off the larvaescientifically known as the slaughter and occupation phasethis invasive species could mean further bad news for the long-suffering U.S. population of honeybee, which, unlike their Asian cousin, have not learned to defend themselves against natural enemies.

Honeybees are an essential pollinator, supporting billions of dollars in crop production annually, however, the global honeybee population is already reeling from Colony Collapse Disorder (CCD). The phenomenon, which is likely caused by an unknown combination of contagions and loss of habitats, has seen a recurring and disconcerting uptick since 2013. Last year alone, CCD reportedly killed off 40% of U.S. honeybee colonies. With this new hornet threat, there could be further devastating consequences for the honeybee-reliant U.S. food supply, already at risk due to the still-raging coronavirus (Covid-19) pandemic.

Although the tech world has made efforts to help on the CCD front, including a number of Israeli companies employing robotics and artificial intelligence,

now, additional innovations will be necessary to deal with the emerging hornet menace.

Many of the methods currently used in Japan to curb the spread of the hornets are low-tech and generally lacking. One novel way to deal with this new-found aggressor, however, may include employing CRISPR gene drives. Succinctly, the method would use CRISPR technology to introduce and then permanently and irreversibly propagate a mutation determinantal to the murder hornets reproduction process, ostensibly wiping out the invasive nests entirely.

The U.S. Department of Defenses Defense Advanced Research Projects Agency (DARPA) and the Bill and Melinda Gates Foundation have, in the past, floated similar proposals to destroy isolated populations of invasive rodents on islands or to wipe out the malaria-causing Anopheles gambiae mosquitoes. Other organizations have taken aim at the Aedes aegypti mosquito, known for transmitting dengue fever, chikungunya, Zika fever, Mayaro, and yellow fever viruses, collectively causing the deaths of millions of people a year, and making hundreds of millions sick. Most recently, in April, a gene drive system was proposed as a tool that could disarm a devastating wheat pathogen.

Gene drives do not always work, even in optimal lab conditions, because life finds a way, so, employing gene drive systems in the wild comes with its own dangers, including the potential for environmental impacts well beyond the researchers initial intentions. For example, some experts fear that gene drive-carrying test organisms might accidentally escape isolated testing areas and be broadly introduced before full testing and analysis can be done.

Active regulatory efforts notwithstanding, there will likely be a European-led call for a moratorium on the release of gene drives this October at the 15th meeting of the Conference of Parties (COP15) to the Convention on Biological Diversity, as per the precautionary policy principle, which calls for constant, arguably innovation-impeding, review when dealing with potentially disastrous new developments.

If, however, we reduce our over-reliance on the precautionary principle, we can look forward to additional productive uses for gene drives in enhancing the security and reliability of the food supply chains. These efforts are increasingly necessary as we will likely see future threats to food production as a result of the growing unpredictability and variability of weather due, in part, to climate change. Genetic engineering, either through gene drives or other innovative methods, can help guide and accelerate the process of developing hardy, stress-resilient, fungi resistantand sustainable foods through making crops more adaptable to harsh weather or by allowing seeds to germinate under even suboptimal growing conditions.

Unfortunately, policy ideals, like the precautionary principle, are still being abused, either due to unfounded fears as a result of misinformationfor example, the notion that the novel coronavirus is a laboratory made disaster and a harbinger of what unregulated genetic engineering can cause or

due to protectionist practices, especially in Europe, arguing for even harsher restrictions on developing genetically modified organisms.

Fortunately, as a growing segment of the population, previously agnostic as to the benefits of scientific endeavors, now looks to science to save it from the pandemic, while even employing CRISPR technologies to fight the virus, we will hopefully see further reduced resistance to genetic innovations, especially when it comes to developments that can save the honeybee population.

In addition to our concern for honey production or our food supply, we should care about the continued existence of bees in general as we can also learn a lot from apiculture. Like us, bees are social creatures that, living in crowded conditions, have learned to rely on good hygienic practices to keep deadly viruses at bay. Last month, researchers studying the deadly (to bees) Israeli acute paralysis virus (IAPV) reported using AI cameras to track how healthy bees avoided their sick brethren, even as the socially irresponsible sick bees themselves actively neglected to socially distance.

And, just like those bees that were examined, we humans will likely also see a huge invasion of privacy as governments aim their AI-enabled cameras on their own citizens to track social distancing compliance. Bees, at least, do not single out Jews or other minority groups or physically hit each other when they fail to comply.

Dov Greenbaum is a director at the Zvi Meitar Institute for Legal Implications of Emerging Technologies, at Israeli academic institute IDC Herzliya.

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How Covid-19 Can Save the World's Bee Population - CTech

BROADALBIN A total of 143 seniors will graduate from Broadalbin-Perth High School in June, and 29 percent have earned a grade point average (GPA) of 90 or better.The top 10 students of the Class of 2020 have achieved GPAs ranging from 96.73 to higher than 100. They vary in their individual interests, talents and plans for the future, but all have demonstrated a commitment to excellence in their education and caring involvement on campus and in the community.The Broadalbin-Perth top 10 students for the Class of 2020 are much more than their tremendous grade point averages, BPHS Principal Mark Brooks said in a news release. They are athletes, musicians and members of numerous extracurricular activities. The accomplishments of this group inside the classroom are truly remarkable. It is what these students have brought to Broadalbin-Perth outside of the classroom and the impact they have had that will be their lasting legacy. I am extremely proud to have such a great group of students at the forefront of our student body.Ttop 10 students of the BPHS Class of 2020:

1.) Miles Compani (100.398 average)Miles may be focused on a career as an industrial engineer with a large, global corporation, but while a student at B-P, he certainly didnt limit his interests. He served as junior varsity and varsity team captain of Masterminds, team mentor of the Future Cities Competition and member of the Science Research Club and First Lego League, and yet he was also co-president of the Esports Club, took part in the Scripps National Spelling Bee and participated in the BPHS Music Improv Group, Jazz Ensemble and Concert Band. Miles community-based activities include Boy Scouts (he is an Eagle Scout and Ad Altare Dei recipient), Mohawk Valley Chamber Ensemble, Gloversville Civic Band and volunteer at the Galway Public Library and Amsterdam Rotary Club. At St. Stephens Church, hes been active as an altar server, lector, member of the fundraising committee and bulletin designer. He is a recipient of the Clarkson Ignite President Fellowship, which provides full tuition for four years; a CASDA 2020 Annual Scholar Award; National Honor Society Scholarship; Future Cities Alumnus of the Year Scholarship; Soroptimist International of Fulton and Montgomery Counties Youth Citizenship Award; Rensselaer Medal Award, and George Washington University Book Award. In the fall, Miles, who is the son of Erin and Todd Compani, will study engineering and management at Clarkson University. When asked what advice he would offer to younger students, Miles said, Be courageous. Dont be afraid to step outside the boundaries of your school and community. Your journey is yours to plan, follow, and achieve as you choose over time, but welcome the unexpected and unknown as they happen.2.) Antonio Zevola (100.294 average)An accomplished student with many interests, Antonio encourages his peers at Broadalbin-Perth High School to expand their horizons. At B-P, he served as president of the National Honor Society and member of the Drama Club, Gay-Straight Alliance Club and Key Club. He was also a member of the cross country and track and field teams. In the community, Antonio volunteered with the Lions Club and worked part-time at Subway. He was awarded the Justice Brandeis Scholarship and SUNY Stony Brook Presidential Scholarship. In the fall, Antonio will enroll at Brandeis University, where he will study computer science and biochemistry. Antonios career aspiration is to become a computational biologist. He is the son of Bibi and Eric Zevola. What advice would Antonio offer to younger students about school? Get involved in everything you can, it really helps expand your social circle, he said. Push yourself out of your comfort zone; youll be surprised what clubs, sports, and activities you end up loving. Dont take everything so seriously; work hard at making sure you are enjoying what you are doing.3.) Matthew Danise (99.203 average)Matthew will head south after graduation: he plans to study finance at Florida State University, where he was awarded an out-of-state tuition scholarship and acceptance into their honors program. His career goal is to become a financial planner. Matthews other awards include a Barrett Honors Scholarship and out-of-state tuition scholarship from Arizona State University and a University Scholars scholarship from Stony Brook University. At B-P, he has been a well-rounded student who credits faculty and staff for their caring and support. Matthew served as Student Government president and member of the Rocket Club and National Honor Society. He was captain of the golf team, where he was a two-time Most Outstanding Player, recipient of the Sean Craig Award and a five-time sectional qualifier. On B-Ps bowling team, he won the Foothills League Tournament highest game award. In his community, Matthew has volunteered at St. Josephs Church, Franklin Community Center, James A. Brennan Memorial Humane Society, and the Capital Region Food Bank. Matthew is the son of Marisa and Ferdinand Ralph Danise. He advises younger B-P students, Do not be afraid to try new clubs and activities. Always reach out to teachers and administrators because they are there to help you.4.) Matthew Syzdek (98.782 average)A leader inside school and on the gridiron, Matthew values tenacity and hard work. At BPHS, he was class president for four years, captain of the football team and has been active in the National Honor Society, Rocket Club, Esports Club and Fishing Club. Matthew was one of B-Ps representatives to the American Legion Boys State. He was an honorable mention on the New York All-State Football team and was named to multiple area all-star football teams. Matt was the first football player in B-P history selected as an overall winner of the National Football Foundations Scholar Athlete Award. Outside of school, Matthew has participated in the Mohawk Valley Chamber Ensemble, the Gloversville Civic Band, and Saint Rose Symphonic Band. He also performed with the area all-state band each of the past two years. Matthew volunteers at the Broadalbin Youth Commissions football clinics and local animal rescues. He is the recipient of a Clarkson Leadership Award, and his career aspiration is to become an engineer. In the fall, Matthew plans to study mechanical engineering at Clarkson University. He is the son of Suzanne and Stephen Syzdek. When asked what advice he would impart to younger students at B-P, Matthew said, My advice would be to never give up. It may get hard, but in the end it is all worth it.5.) Avery Fenton (98.764 average)Avery took on the world, literally, while a student at B-P. In 2018 and 2019, she and fellow members of B-Ps Odyssey of the Mind team won first place in state competition and then finished in the top five at the World Finals, an international competition. Avery received the OMER award for volunteering to help other Odyssey teams and for competing for eight years, and the Odyssey of the Mind Ranatra Fusca Award for extraordinary creativity of solution. She was a cheerleader at football, basketball and competition events and served as cheerleading captain during her senior year, when she was named to the 2020 Foothills Council Cheerleading Allstar Second Team Backspot position. Avery was also awarded a Dedication Award and a Sportsmanship Award in cheerleading. Her other honors include the University of Rochester Xerox Award. In her community, Avery served as 1st Sunday school teacher at St. Josephs Church, assisted with the Broadalbin Youth Commission Little Leagues concession stand and volunteered at Fish House Community Center events. Avery has enrolled in Fairfield University for General Nursing Studies and is considering a career in healthcare as a nurse anesthetist. She is the daughter of Christopher and Julie Fenton. To younger students in school, she advises, Get involved as much as you can. High school will be one of the best times in your life, so take advantage of every opportunity there is. These years go by in the blink of an eye, make them count.6.) Sydney Rogers (98.155 average)Sydney played sports, was active in clubs, worked part-time, volunteered all while excelling in her classes as a student at BPHS. Sydneys ability to balance many interests will surely prove beneficial when she pursues a future career in medicine. Next fall, she plans to attend Fairfield University, where she was accepted into the honors program and will study biology. In recognition of her achievements, Sydney was awarded the Magis Scholarship for Fairfield University, a renewable, four-year award. At B-P, Sydney served as treasurer of the National Honor Society, and class secretary while she was in grades 10, 11 and 12. She also played softball, was captain of the varsity volleyball team and was honored with the Coachs Award, Allstar Team for volleyball. Outside of school, Sydney worked at Town and Country Deli and has volunteered for the Saratoga Palio Half Marathon. The daughter of Michael and Jennie Rogers, Sydney is reflective about the experience of todays young people during a time of pandemic. When asked what advice she would offer younger students in her school, Sydney said, We have seen with the coronavirus that things dont happen as you expect them to. Appreciate the little moments, and dont take your time at school for granted.7.) Madison Fariello (97.750 average)Madison urges her younger peers to have a range of experiences, advice she can vouch for. At B-P, she has been active as Student Council co-vice president, Lions Club student liaison, and member of the National Honor Society, Key Club, Spanish Club and Drama Club. Shes played club volleyball, varsity volleyball and served as varsity team co-captain. She earned the NYSPHSAA Girls Volleyball Championships Sportsmanship Award, B-P Varsity Volleyball Coachs Award, and Section 2 First Team and Second Team awards. Madison was also a member of B-Ps track and field team. Outside of school, Madison has volunteered at Nathan Littauer Hospital as a candy striper/junior volunteer and at St. Marys Institute Drama Program and Summer Camp, Red Cross Blood Drives, Color Runs and the Summer Drama Program. She has worked at The Flower Bed and Pizza Supreme. Madison has been on the B-P Principals List all four years of high school, and she has been awarded the Rochester Institute of Technology Computing Medal Scholarship, Le Moyne College Presidential Scholarship, Hofstra University Presidential Scholarship and Syracuse University Award of Recognition. She plans enroll in college to study medicine, with a career goal of working in dermatology. She is deciding between Northeastern University, Penn State University, Hofstra University, and Fairfield University. Madison is the daughter of Allison and Michael Fariello. When asked what advice she would offer to younger students about school, Madison said, Take advantage of as many opportunities as possible. Its important to be yourself and diversify your experiences as much as you can, despite the discomfort you may feel. As long as youre trying your best, you should be proud of what you achieve.8.) Eric Vertorano (97.709 average)Eric was voted Most Spirited four years in a row during pep rally at BPHS. His energy, involvement and school spirit are certainly evident in his accomplishments and activities during his high school years. Eric has served as vice president and treasurer of Spanish Club, as class officer, secretary and treasurer of Key Club, and as a member of the National Honor Society. He was also a main set designer in Drama Club and is recipient of that clubs Helping Hands Award. Erics other honors include the Fredrick Douglass and Susan B. Anthony Award from the University of Rochester. Outside of school, Eric participated in the Capital Region Institute for Human Rights 2019 Teen Summer Symposium and the H.O.B.Y. Leadership Conference. He also has volunteered at the James A. Brennan Memorial Humane Society. Eric is enrolled at the University of Rochester, where he plans to study international relations and Spanish. His career aspiration is to work in the field of international law. Eric is the son of Michael and Michelle Vertorano. Being present is at the heart of his advice for younger students. Attendance is key, Eric said. Be there every day, physically and mentally.9.) Emily Macfarlane (97.692 average)Emily has volunteered more than 300 hours St. Marys Hospital, an impressive amount of time given her many other activities while a student at B-P. Her volunteer experience will also likely add perspective to her study of biomedical engineering in college. She is considering the University at Buffalo and aspires to a career as a genetic engineer or geneticist. In high school, Emily served as a class officer in Key Club and treasurer in Band. She was active as a member of the National Honor Society, Masterminds, Research Club and STEM Club. She also played on the soccer team at BPHS. Emilys achievements have earned her a Semler Fidelitys Excellence in Band Award and a George Eastman Young Leaders Award. Emily is the daughter of Heather and Todd Macfarlane. When asked what advice she would offer to younger students about school, Emily said, You should always do your work on time, and dont procrastinate. If youre struggling then you should get the help you need.10.) Meaghan Uhlinger (96.730 average)Meaghan is an accomplished Scholar Athlete and well-rounded student who cherishes the times she spent on campus with her friends and fellow students throughout her years at B-P. Meaghan earned the Scholar Athlete award for each of her varsity seasons. She was involved in cheerleading for football, basketball and competition, where she was honored as a three-time Section 2 runner up, and she also participated in outdoor track and field. Meaghan served as co-president of Band, was active as a member of Masterminds, Key Club, National Honor Society, and during her freshman year, of the Wind Turbine Team. In the community, Meaghan has volunteered with the fundraising walk for the American Foundation for Suicide Prevention and the Relay for Life event benefiting the American Cancer Society, and she has worked part-time at TJ Maxx. In honor of her all of her achievements, Meaghan was awarded an Elmira Key Scholarship. She plans to study criminology this fall at SUNY Cortland, with a career goal of working in law enforcement. Meaghan is the daughter of Jamie and Corey Uhlinger. In light of todays changing times due to the coronavirus pandemic, Meaghan advises younger students to, Cherish the time you have at Broadalbin-Perth. These circumstances have taught me how grateful I should have been to see my friends five times a week at school, so enjoy every day you are in the building with your peers.

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B-P names Top 10 students in Class of 2020 - The Recorder

The relationship between the coronavirus and human genetics is murky.

When some people become infected with the coronavirus, they only develop mild or undetectable cases of COVID-19. Others suffer severe symptoms, fighting to breathe on a ventilator for weeks, if they survive at all.

Despite a concerted global scientific effort, doctors still lack a clear picture of why this is.

Could genetic differences explain the differences we see in symptoms and severity of COVID-19?

To test this, we used computer models to analyze known genetic variation within the human immune system. The results of our modeling suggest that there are in fact differences in peoples DNA that could influence their ability to respond to a SARS-CoV-2 infection.

When a virus infects human cells, the body reacts by turning on what are essentially anti-virus alarm systems. These alarms identify viral invaders and tell the immune system to send cytotoxic T cells a type of white blood cell to destroy the infected cells and hopefully slow the infection.

But not all alarm systems are created equal. People have different versions of the same genes called alleles and some of these alleles are more sensitive to certain viruses or pathogens than others.

A model of an HLA protein (green and yellow) bound to a piece of a virus (orange and blue) in this case, influenza. Prot reimage via Wikimedia Commons, CC BY-SA

To test whether different alleles of this alarm system could explain some of the range in immune responses to SARS-CoV-2, we first retrieved a list of all the proteins that make up the coronavirus from an online database.

We then took that list and used existing computer algorithms to predict how well different versions of the anti-viral alarm system detected these coronavirus proteins.

The part of the alarm system that we tested is called the human leukocyte antigen system, or HLA. Each person has multiple alleles of the genes that make up their HLA type. Each allele codes for a different HLA protein. These proteins are the sensors of the alarm system and find intruders by binding to various peptides chains of amino acids that make up parts of the coronavirus that are foreign to the body.

Once an HLA protein binds to a virus or piece of a virus, it transports the intruder to the cell surface. This marks the cell as infected and from there the immune system will kill the cell.

In general, the more peptides of a virus that a persons HLAs can detect, the stronger the immune response. Think of it like a more sensitive sensor of the alarm system.

The section of DNA that codes for HLAs is on the sixth chromosome. Pdeitiker at English Wikipedia / Wikipedia, CC BY

The results of our modeling predict that some HLA types bind to a large number of the SARS-CoV-2 peptides while others bind to very few. That is to say, some sensors may be better tailored to SARS-CoV-2 than others. If true, the specific HLA alleles a person has would likely be a factor in how effective their immune response is to COVID-19.

Because our study only used a computer model to make these predictions, we decided to test the results using clinical information from the 2002-2004 SARS outbreak.

We found similarities in how effective alleles were at identifying SARS and SARS-CoV-2. If an HLA allele appeared to be bad at recognizing SARS-CoV-2, it was also bad at recognizing SARS. Our analysis predicted that one allele, called B46:01, is particularly bad with regards to both SARS-CoV-2 and SARS-CoV. Sure enough, previous studies showed that people with this allele tended to have more severe SARS infections and higher viral loads than people with other versions of the HLA gene.

Based on our study, we think variation in HLA genes is part of the explanation for the huge differences in infection severity in many COVID-19 patients. These differences in the HLA genes are probably not the only genetic factor that affects severity of COVID-19, but they may be a significant piece of the puzzle. It is important to further study how HLA types can clinically affect COVID-19 severity and to test these predictions using real cases. Understanding how variation in HLA types may affect the clinical course of COVID-19 could help identify individuals at higher risk from the disease.

To the best of our knowledge, this is the first study to evaluate the relationship between viral proteins across a wide range of HLA alleles. Currently, we know very little about the relationship between many other viruses and HLA type. In theory, we could repeat this analysis to better understand the genetic risks of many viruses that currently or could potentially infect humans.

Written by Austin Nguyen, PhD Candidate in Computational Biology and Biomedical Engineering at Oregon Health & Science University, Abhinav Nellore, Assistant Professor of Biomedical Engineering & Surgery at Oregon Health & Science University, and Reid Thompson, Assistant Professor of Radiation Medicine at Oregon Health & Science University.

Originally published on The Conversation.

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Whether the Coronavirus Puts You in the Hospital Could Depend on Your Genes And Were Unraveling Which Ones Matter - SciTechDaily

Westport, CT, May 05, 2020 (GLOBE NEWSWIRE) -- BioSig Technologies, Inc. (NASDAQ: BSGM) (BioSig or the Company) today appointed Mr. Dennis Purcell to the Board of Directors of its majority-owned subsidiary ViralClear Pharmaceuticals, Inc.

Mr. Purcell brings to ViralClear a wealth of life science and investment experience. Mr. Purcell is the Founder of Aisling Capital LLC and previously served as Senior Managing Partner. Prior to Aisling Capital, Mr. Purcell served as Managing Director of the Life Sciences Investment Banking Group at Chase H&Q (formerly Hambrecht & Quist, H&Q). Aisling Capital (formerly Perseus-Soros Bio-pharmaceutical Fund), formed in 2001, is a leading venture capital fund that has invested over $2 billion in emerging biopharmaceutical companies globally which has helped the industry to mature and become the main source of new innovative drugs and devices being used to treat diseases today. While at H&Q, Mr. Purcell was directly involved with over two hundred completed transactions and supervised over $10 billion of financing and advisory assignments in the Life Sciences industry. Prior to joining H&Q, Mr. Purcell was a Managing Director in the Healthcare Group at PaineWebber, Inc.

Mr. Purcell is a frequent commentator on the industry and has been honored in the Biotech Hall of Fame by Genetic Engineering News, named to the Biotechnology All-Stars list by Forbes ASAP, honored as one of the top 50 Irish-American businessmen and cited as one of the top 100 contributors to the biotechnology industry.

Mr. Purcell serves on numerous healthcare company boards. He currently sits on the Boards of Real Endpoints, Summus Global, Inc., BioScience Managers Pty Ltd., and Ichnos Sciences. He also serves as a member of the Board of: the Editorial Advisory Board at Life Science Leader Magazine; the Executive Committee at NYBIO Association; the University of Delaware Investment Visiting Committee as well as the Biopharmaceutical Innovation Board at the University of Delaware; the Foundation of the Alliance for Regenerative Medicine; and the Healthcare sector of the New York City Investment Fund. He is also an Executive in Residence at Columbia University.

Mr. Purcell received his M.B.A. from Harvard Business School and his B.S. in Accounting from the University of Delaware.Mr. Purcell is the latest high-profile addition to the Companys Board and will serve alongside former Chief Medical Officer of Celgene Jerome Zeldis, M.D., Ph.D, Nick Spring, CEO of ViralClear and a former senior executive at Merck & Co. and Anthony Zook, former senior executive at Astra Zeneca, Plc.

ViralClear assembled a team with a highly impressive collective skillset to address a very pressing public health issue. I look forward to joining the management and my fellow Board members as the Company seeks to translate the strong in vitro findings into clinically meaningful results, commented Mr. Purcell.

We are thrilled to welcome Dennis at this important time in our Companys development, and look forward to his contributions, added Jerome Zeldis, M.D., Ph.D, Executive Chair of ViralClear Pharmaceuticals, Inc.

The Company recently announced that Mayo Clinic is set to become a study site for a planned Merimepodib Phase II clinical trial for the treatment of COVID-19, once permitted by the FDA. The study will be a randomized, placebo-controlled trial. Data from the Phase II trial is expected within three months from its commencement.

Dennis is a fantastic addition to ViralClear Board. His extensive knowledge of the biotech industry and his directorship expertise will be highly valuable to the Company as it reaches inflection points in its development, stated Kenneth L. Londoner, Chairman and CEO of BioSig Technologies, Inc. and Director of ViralClear Pharmaceuticals, Inc.

About merimepodibAnti-viral candidate merimepodib (MMPD) targets RNA-dependant polymerases. The molecule has shown activity against a broad spectrum of RNA viruses and has demonstrated satisfactory safety data from over 300 patients treated for hepatitis C. Recently, the Company published first pre-clinical data generated under contract with Galveston National Laboratory at The University of Texas Medical Branch. The Company recently submitted two manuscripts titledThe IMPDH inhibitor merimepodib provided in combination with the adenosine analogue remdesivir reduces SARS-CoV-2 replication to undetectable levels in vitro and The IMPDH inhibitor merimepodib suppresses SARS-COV-2 replications. The manuscripts were authored by Natalya Bukreyeva, Emily K. Mantlo, Rachel A. Sattler, Cheng Huang, John T. Manning, Slobodan Paessler, DVM, Ph.D of the UTMB Galveston National Laboratory and Jerome Zeldis, M.D., Ph.D of ViralClear. In-vitro studies referenced in the manuscript demonstrated that merimepodib decreased viral production by over 98%.

About BioSig TechnologiesBioSig Technologies is a medical technology company commercializing a proprietary biomedical signal processing platform designed to improve signal fidelity and uncover the full range of ECG and intra-cardiac signals (www.biosig.com).

The Companys first product, PURE EP(tm) System is a computerized system intended for acquiring, digitizing, amplifying, filtering, measuring and calculating, displaying, recording and storing of electrocardiographic and intracardiac signals for patients undergoing electrophysiology (EP) procedures in an EP laboratory.

About ViralClearBioSigs subsidiary ViralClear Pharmaceuticals, Inc., is seeking to develop a novel pharmaceutical to treat COVID-19. Merimepodib is intended to be an orally administered, broad-spectrum anti-viral agent that has demonstrated strong activity against COVID-19 in cell cultures in laboratory testing. The product candidate has completed Phase I and three Phase II trials in other indications.

Forward-looking Statements This press release contains forward-looking statements. Such statements may be preceded by the words intends, may, will, plans, expects, anticipates, projects, predicts, estimates, aims, believes, hopes, potential or similar words. Forward- looking statements are not guarantees of future performance, are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Companys control, and cannot be predicted or quantified and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks and uncertainties associated with (i) the geographic, social and economic impact of COVID-19 on our ability to conduct our business and raise capital in the future when needed, (ii) our inability to manufacture our products and product candidates on a commercial scale on our own, or in collaboration with third parties; (iii) difficulties in obtaining financing on commercially reasonable terms; (iv) changes in the size and nature of our competition; (v) loss of one or more key executives or scientists; and (vi) difficulties in securing regulatory approval to market our products and product candidates. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Companys filings with the Securities and Exchange Commission (SEC), including the Companys Annual Report on Form 10-K and its Quarterly Reports on Form 10-Q. Investors and security holders are urged to read these documents free of charge on the SECs website at http://www.sec.gov. The Company assumes no obligation to publicly update or revise its forward-looking statements as a result of new information, future events or otherwise.

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Biotech and Investment Veteran Dennis Purcell Joins the Board of ViralClear Pharmaceuticals, a majority-owned subsidiary of BioSig Technologies, Inc....

University of Waterloo biology professor Kathleen Hill co-led a team of researchers whove identified an underlying genomic signature for 29 different COVID-19 sequences. They did this using a new graphics-based software classification tool powered by machine learning. When sequencing the genome of a virus like COVID-19, the classification software makes use of a decision tree method to run through the best possible choices and achieve a 100 percent accurate outcome within minutes.

This is a 3D map of researchers' machine learning classification tool. (a) 3,273 viral sequences from the researchers first test, representing 11 viral families and realm Riboviria; (b) 2,779 viral sequences from the second test, classifying 12 viral families of realm Riboviria; and (c) 208 Coronaviridae sequences classified into genera. (Image courtesy of PLOS.)

Researchers wrote a paper about their findings called Machine learning using intrinsic genomic signatures for rapid classification of novel pathogens: COVID-19 case study. According to the paper, The proposed method combines supervised machine learning with digital signal processing (MLDSP) for genome analyses, augmented by a decision tree approach to the machine learning component, and a Spearmans rank correlation coefficient analysis for result validation. These tools are used to analyze a large dataset of over 5000 unique viral genomic sequences, totaling 61.8 million bp, including the 29 COVID-19 virus sequences available on January 27, 2020.

The teams results confirm the currently accepted hypothesis that COVID-19 (SARS-CoV-2) originated from bats, and their results classified it as Sarbecovirus within Betacoronavirus. The findings suggest that their machine learning approach is a reliable, scalable and quick option for taxonomic classification of novel viruses. This means that the tool can be used to better serve real-time worldwide reaction and strategy to combat novel viruses in the future.

Mobilizing medical personnel to react as quickly as possible is invaluable in the fight against a global pandemic and will also be incredibly useful in helping develop correct treatments to outbreaks of novel viruses, including the rapid development of vaccines.

Bottom Line

The research is encouraging for future outbreaks, but what it means for the treatment and rapid development of vaccines for the COVID-19 outbreak remains unclear. New studies are showing the efficacy of Remdesivir in treating patients infected with COVID-19, and two vaccinations from Oxford and Germany that seem to be making rapid progress are set to begin human trials in the coming months. Lets hope for the best.

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Researchers Develop New Classification Tool to Find COVID-19 Genetic Signature - ENGINEERING.com

There are four animals that have become relevant in the context of the coronavirus disease (Covid-19). This column is about them.

It was only in 2013, after a decade of looking for the source of the Sars-CoV (or Sars-CoV-1) virus that causes the Severe Acute Respiratory Syndrome, that scientists found the natural host of the virus, horseshoe bats specifically, horseshoe bats in a cave outside a large city in Chinas Yunnan province. Somehow, the virus had made the jump from the bats, to civets in Guangdong, and from them to humans (the Chinese eat civet meat and the first people to be infected were wildlife traders from Guangdong). A fascinating article in Scientific American in March narrated this quest as part of its profile of Shi Zhengli, a virologist in Wuhan. Scientists say the bats may well be the natural host of the virus that causes the coronavirus disease too.

Horseshoe bats, then, are the first animals of relevance in the context of Covid-19. That shouldnt surprise anyone. Research has established that bats are hosts to more zoonoses (pathogens that can cross over to humans, causing an infection) than any other species.

Sometimes, the transmission happens directly. Sometimes, it happens through another animal. In the case of Sars, it was the masked palm civet that was the intermediary. In the case of the Middle East Respiratory Syndrome, or Mers, it was a species of camel. In the case of Covid-19, scientists believe the intermediary was the pangolin specifically, the Malayan Pangolin. India has a species of pangolin too, the Indian Pangolin. Pangolins are widely used in Chinese medicine, so its easy to see how Sars-CoV-2 could have jumped from bats to pangolins to humans.

The pangolin, then is the second animal of relevance in the context of Covid-19, which, as of Thursday, has infected 3.8 million people, and killed 265,000 (of the 3.8 million, 1.3 million have recovered).

The global scale of the pandemic, which has no cure right now, has meant everyone knows the significance of ChAdOx1 nCoV-19. This is the vaccine being developed at the University of Oxford. The vaccine hopes to tackle Covid-19 by injecting a weakened adenovirus into which genetic material from Sars-CoV-2 has been inserted something that should generate an immune response. The adenovirus the scientists at Oxford are using is one that causes cold in chimpanzees, which explains the name of the vaccine (Ch for chimpanzee and Ad for adenovirus). We humans share 99% of our DNA with chimpanzees and bonobos (another ape, and one that belongs to the same genus as chimpanzees).

Chimpanzees are the third animal of relevance in the context of Covid-19, especially given that ChAdOx1 nCoV-19 remains our best bet yet. There are expectations that it will be available this year itself, and Indias Serum Institute has already started making it taking a bet that an ongoing clinical trial will work.

But chimpanzees arent the only potential saviours of the human race. Over the past two days, there has been a lot of focus on llamas, the ungulates with pretty eyelashes. It turns out that they have antibodies that can tackle Covid-19 (the findings of a study on this were published earlier this week on the respected journal, Cell). It also turns out that the antibodies produced by llamas can be merged with antibodies produced by other species, including humans. Indeed, research has shown that all other members of the family llamas belong to, camelidae, produce antibodies with the same property they are stable at higher temperatures, and lend themselves to genetic engineering because of their small size.

The llama, then, is the fourth animal of relevance in the context of the pandemic. And if llamas hold the answer to the virus, they will become as famous as the horses that helped humankind in the fight against diphtheria -- but thats another story.

More here:
Covid-19: What you need to know today - Hindustan Times

This article originally appeared on The Conversation. You can read it here.

Scientists are constantly revealing newly discovered benefits of exercise. In experiments over the past 10 years, my research has found that exercise can help with a respiratory problem known as ARDS.

ARDS is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs that prevents oxygen from reaching the organs. It has been reported in many COVID-19 patients.

I am an exercise physiologist with training in medicine. More than 30 years ago, I gave up my career in general surgery in China and came to the U.S. to pursue a basic research career in molecular exercise physiology, as I was intrigued by the superb health benefits of regular exercise.

Most recently I've been thinking about the potential impact of regular exercise in preventing this deadly complication of COVID-19. I have not done any experiments specifically around COVID-19, but my work with mice may inform other researchers exploring ways to protect people that suffer from ARDS.

A cause of death for 3%-17% of patients infected with SARS-CoV-2 is ARDS. COVID-19 patients with this dismal clinical complication have a mortality rate of greater than 50%.

Specifically, ARDS can occur when viral infection of the cells in the lungs activates the immune system and attracts white blood cells to travel through the bloodstream to the lung tissue to fight off the viral infection.

However, when too many white blood cells appear in the lung tissue at once, it can cause lung tissue damage. This is because they produce too much of damaging molecules called free radicals which break proteins, the cell membrane and DNA.

As a consequence, the blood vessels in the lung become leaky, causing accumulation of the fluid in the lung tissue, and the air sacs of the lung fill up with fluid. This prevents those same air sacs, called alveoli, from filling with air, blocking oxygen in the air from getting into the blood. Patients die of oxygen deprivation.

The cells that line our blood vessels are flat-shaped endothelial cells. One early step in this complicated ARDS disease process is the lining of the blood vessel becomes sticky to white blood cells by making sticky proteins on the cell surface, a phenomenon called endothelial cell activation.

This triggers a vicious cycle; the greater endothelial cell activation, the more free radicals the white blood cells release. This in turn destroys the endothelial cells, making the blood vessel leak more and damages lung tissue.

More than 10 years ago, I started to study the protective role of exercise-induced antioxidant enzymes against loss of muscle size. My research has shown that endurance exercise promotes production of an antioxidant called extracellular superoxide dismutase (EcSOD) that breaks down the free radical superoxide outside of the cells.

EcSOD is the only antioxidant enzyme that is secreted into the blood that reaches other vital organs and binds to the endothelial cells and other cells through a unique binding structure of the enzyme. This makes EcSOD unlike any supplemental antioxidant pill or food rich in antioxidants that we may consume. An oral antioxidant, once absorbed into the blood, does not target a given organ to provide protection, while EcSOD sticks to specific organs.

When I first saw the evidence of increased EcSOD in skeletal muscle by aerobic exercise training, I was inspired to do an experiment in which I tested whether just increasing the amount of this enzyme through genetic engineering, instead of naturally through exercise, would provide protection from various diseases in which free radicals are known to play important roles, such as muscle atrophy and heart failure.

I engineered a mouse that produced more EcSOD in skeletal muscle than would the typical mouse to mimic the effects of aerobic exercise training. We obtained clear evidence that these mice were protected from muscle atrophy and diabetes-induced heart failure.

I then artificially triggered ARDS in mice by injecting mice with a chemical produced by bacteria that are known to cause this condition. To my pleasant surprise, genetically engineered mice with higher concentrations of EcSOD in their blood were far more likely to survive the severe ARDS and multiple organ failure compared with a dismal mortality in the typical mice. This mimics the situation in intensive care where more than 80% of the patients die when they suffer from the failure of multiple organs, including ARDS.

I then confirmed that indeed it was the EcSOD in the genetically engineered mice that provided the protection. When I performed an experiment in which a genetically engineered mouse shared blood with a normal mouse following a surgical procedure called parabiosis, or I took blood from a mouse with high EcSOD and transfused it into a normal mouse suffering from ARDS, the normal mouse had reduced severity of ARDS and clinical blood markers of multiple organ failure. Using various biochemical and imaging technologies, we saw the evidence of reduced endothelial cell activation and reduced protein, cell membrane and DNA damage caused by free radicals in the lung tissue.

These studies have provided proof-of-principle evidence that delivery of the EcSOD gene or protein to elevate the amount of EcSOD in the blood and vital organs may be an effective intervention for protection of the lungs and other vital organs against damages caused by ARDS and multiple organ failure.

My findings in mice may inspire other researchers to come up with innovative ways to prevent and treat the deadly complication of COVID-19.

For example, future studies may identify the exercise type, intensity and duration to optimally increase EcSOD levels in the lungs and other vital organs in humans to build up the defense against deadly complications of COVID-19 or other disease conditions. Of course, the findings may inspire research to foster pharmacological, protein and or gene therapies to treat COVID-19 patients with ARDS.

The EcSOD antioxidant story is just one of many about the health benefits of exercise. I believe we can learn from exercise to develop effective therapies to treat ARDS caused by COVID-19 and other disease conditions.

Zhen Yan is Professor of Cardiovascular Medicine, University of Virginia

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Exercise may help reduce the risk of deadly COVID-19 complication - GOOD Magazine