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Archive - 2020

Date

May 17th

New Technology (RADICL-Seq) Reveals How RNAs, Particularly Long-Noncoding RNAs (lncRNAs), Regulate Gene Activity; RIKEN-Developed RADICL-Seq Will Allow “Deeper Understanding of the Fine Regulatory Network Governing Gene Expression”

The discovery of a huge number of long non-protein-coding RNAs (lncRNAs) in the mammalian genome was a major surprise of the recent large-scale genomics projects. An international team, led by scientists at Japan’s RIKEN Center for Integrative Medical Sciences, and including a bioinformatician from the Research Center of Biotechnology of the Russian Academy of Sciences, and the Moscow Institute of Physics and Technology (MIPT), has developed a reliable method for assessing the role of such RNAs. The new technique and the data obtained with it allow the generation of important hypotheses on how chromatin is composed and regulated, as well as identifying the specific functions of lncRNAs. Presented in an article published on February 24, 2020 in Nature Communications, the technology is called RADICL-seq and enables comprehensive mapping of each RNA, captured while interacting with all the genomic regions that it targets, where many RNAs are likely to be important for genome regulation and structure maintenance. The open-access article is titled “RADICL-Seq Identifies General and Cell Type–Specific Principles of Genome-Wide RNA-Chromatin Interactions.” It was previously believed that RNA functions mostly as an intermediary in building proteins based on a DNA template, with very rare exceptions such as ribosomal RNAs. However, with the development of genomic analysis, it turned out that not all DNA regions encode RNA, and not all transcribed RNA encodes proteins. Although the number of noncoding RNAs and those that encode proteins is about the same, the function of most noncoding RNA is still not entirely clear.

Rockefeller University Scientists Investigate Life-Threatening Kawasai-Like Inflammation Affecting Some Children with COVID-19

Although the coronavirus has largely spared the young, some children who have been infected with SARS-CoV-2 become seriously ill with inflammation of the heart and blood vessels. In New York, at least 5 children have died and over 100 cases, mostly school-aged children, with this syndrome have been identified, according to the state. Like much about the virus, the link between the coronavirus and the disease is a mystery, and public health officials are eager to understand what makes certain children susceptible. In a May 15, 2020 press release, it was announce that Rockefeller University scientists have partnered with the New York State Department of Health (https://www.governor.ny.gov/news/governor-cuomo-announces-state-helping-...) in an effort to learn how the mysterious and frightening illness develops. Using gene sequencing technologies, the new study will search for genetic similarities between patients that may shed light on its pathogenesis. “We may find a genetic clue that could help explain what is driving this severe complication in these children, which can, in turn, inform their clinical care,” says Jean-Laurent Casanova, MD, PhD, Head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University. As part of an international study (https://www.covidhge.com/) of genetic causes behind severe COVID-19 in young people (https://www.rockefeller.edu/news/28008-gene-hunt-explain-young-healthy-p...), Dr. Casanova and collaborators have been enrolling these unusual cases since early March, when they were first reported by European doctors. Collaborating with the New York Genome Center (https://www.nygenome.org/) and the state’s health department to investigate the New York cases, as well as cases reported worldwide, will provide Dr.

May 16th

SAB’s Rapid Response to COVID-19; Company Has Engineered Cows to Contain Full Set of Human Antibody Genes; DoD & BARDA Grant SAB >$16 Million for Preclinical & Manufacturing Studies of SAB-185, Company’s Cow-Derived Human Polyclonal Antibody for COVID-19

In an April 24, 2020 article in BioCentury, it was reported that SAB Biotherapeutics in Sioux Falls, South Dakota, had already been working with the U.S. Department of Defense (DoD) to prepare itscow-based human polyclonal antibody platform for rapid responses to new infectious diseases when COVID-19 emerged. The company has since applied its DiversitAb platform to generate SAB-185, a cow-derived human polyclonal antibody therapy that the company says is more consistent and easier to scale up than convalescent plasma from recovered COVID-19 patients. SAB Co-Founder and CEO Eddie Sullivan told BioCentury that the company expects initial lots of SAB-185, which targets the SARS-CoV-2 spike protein, to be ready for clinical testing in early summer. The DoD had granted SAB a three-year contract, starting in September, 2019, for up to $27 million to develop and test a rapid-response antibody program to counter biological threats. Prior to the COVID-19 outbreak, the company had begun work on building out its antibody platform and scaling up its manufacturing process. SAB’s DiversitAb platform generates human polyclonal antibodies in cows that have been genetically engineered to contain the full set of human antibody genes [see “SAB: Human Polyclonal Antibodies on the Hoof” (https://www.biocentury.com/article/302044)]. “None of us, when we started the contract, expected that we would have a worldwide pandemic on our hands during the time that we’re trying to work with the Department of Defense and build the technology in order to be able to rapidly respond,” said Sullivan.

Huda Zoghbi & Sir Adrian Bird Share World’s Largest ($1.5 Million) & Most Prestigious Prize for Pioneering Brain Research for Their Seminal Work on Rett Syndrome

Huda Zoghbi (https://www.bcm.edu/people/view/huda-zoghbi-m-d/b1855108-ffed-11e2-be68-...), MD, Professor and Howard Hughes Medical Institute Investigator at Baylor College of Medicine and Director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, has been awarded what is considered one of the world’s most prestigious prizes in brain research, Denmark’s Lundbeck Foundation Brain Prize. Dr. Zoghbi is being awarded, along with Sir Adrian Bird from the University of Edinburgh, UK. Both are being honored for their work on Rett syndrome that has led to a better understanding of the disorder and brought researchers closer to a treatment. The Brain Prize, which includes research funding, is given once a year in recognition of a researcher’s unprecedented contribution to international brain research. The recipient(s) is/are nominated by their peers and decided on by a panel of the world’s top neurological researchers. Established in 2010, the Brain Prize is awarded by Denmark's largest private funder of neuroscience research, the Lundbeck Foundation. In only a few years, the Prize has become known as the most distinguished neuroscience prize in the world. Prize winners are awarded DKK 10 million, which is approximately €1 million or $1.5 million. “I am deeply honored and humbled to receive this prize and to share this honor with Adrian Bird. This recognition means a lot to me on many levels. It shows support to the families living with Rett syndrome and to my trainees who work tirelessly on this research,” Dr. Zoghbi said. “This will allow us to take risks and push the research forward to find a treatment.” “Dr. Huda Zoghbi stands out as a leader in this field of research.

UK Government Awards $600,000 for Trial of Dogs Detecting Odor of COVID-19; Previous Success with Malaria Noted; Dog’s Nose May Prove “Game-Changer” in Screening for COVID-19; Novel Approach Could Enable Rapid Screening of High Numbers of People

On May 15, 2020, it was announced that the UK Government has awarded a specialist team of researchers more than £500,000 (~$600,000) to find out if specially-trained bio-detection dogs can be used as a rapid, non-invasive testing measure for COVID-19. In the first phase of the trial, world-leading disease control experts from the London School of Hygiene & Tropical Medicine (LSHTM), in collaboration with experts at Medical Detection Dogs (https://www.medicaldetectiondogs.org.uk/) and UK’s Durham University, aim to determine whether dogs are able to detect coronavirus in humans from odor samples. This team has previously worked together to demonstrate that dogs can detect odors from humans with a malaria infection with extremely high accuracy – above the World Health Organization (WHO) standards for diagnostic. This new trial will look at whether dogs can be trained to detect coronavirus, even if people are asymptomatic. If the trial gathers sufficient evidence, the first set of dogs could be deployed to key points of entry into the UK within six months to assist with the rapid screening of people travelling from abroad. If successful, these dogs could provide a fast and non-invasive detection method alongside the Government’s robust five-pillar testing strategy (https://www.gov.uk/government/publications/coronavirus-covid-19-scaling-...), potentially screening up to 250 people per hour each. It is one of a number of testing measures being explored in order to ensure the Government’s response to the virus is as extensive as possible.

May 15th

Genome-Wide Pattern Found in Tumors from Brain Cancer Patients Predicts Life Expectancy; Proof-of-Principle Study Highlights Mathematical Methods That Are Uniquely Suited for Personalized Medicine

For the past 70 years, the best indicator of life expectancy for a patient with glioblastoma (GBM)--the most common and the most aggressive brain cancer--has simply been age at diagnosis. Now, an international team of scientists has experimentally validated a predictor that is not only more accurate, but also more clinically relevant: a pattern of co-occurring changes in DNA abundance levels, or copy numbers, at hundreds of thousands of sites across the whole tumor genome. Patients with the genome-wide pattern survive for a median of one year. However, patients without it survive three times as long, for a median of three years. The results came from a retrospective clinical trial that was published online on May 15, 2020 in Applied Physics Letters (APL) Bioengineering (https://aip.scitation.org/doi/10.1063/1.5142559). The open-access article is titled “Retrospective Clinical Trial Experimentally Validates Glioblastoma Genome-Wide Pattern of DNA Copy-Number Alterations Predictor of Survival.” Having a predictor of a patient's life expectancy can help inform medical decisions. The GBM pattern can, in principle, be used in this way today. For example, when a patient has magnetic resonance imaging results that are inconclusive, such information can help doctors decide whether to perform an intervention. "The information contained in this pattern, and other patterns that we can discover by using the same mathematical methods, can improve the standard of care of GBM and other diseases," said the team leader Orly Alter (photo), PhD, Utah Science, Technology, and Research (USTAR) Associate Professor of Bioengineering and Human Genetics at the Scientific Computing and Imaging Institute and the Huntsman Cancer Institute at the University of Utah.

Treatment with Interferon-α2b Speeds Recovery of COVID-19 Patients in Exploratory Study

Treatment with antivirals such as interferons may significantly improve virus clearance and reduce levels of inflammatory proteins in COVID-19 patients, according to a new study published online on May 15, 2020 inn Frontiers in Immunology. The article is titled “Interferon-Alpha2b Treatment for COVID-19.” Researchers conducting an exploratory study on a cohort of confirmed COVID-19 cases in Wuhan found that treatment with interferon (IFN)-α2b significantly reduced the du-ration of detectable virus in the upper respiratory tract and reduced blood levels of interleukin(IL)-6 and C-reactive protein (CRP), two inflammatory proteins found in the human body. The findings show potential for the development of an effective antiviral intervention for COVID-19, which is an ongoing global pandemic caused by the novel coronavirus, SARS-CoV-2. "Interferons are our first line of defense against any and all viruses - but viruses such as corona-viruses have co-evolved to very specifically block an interferon response", says lead author Eleanor Fish (photo), PhD, of the Toronto General Hospital Research Institute & University of Toronto's Department of Immunology, adding: "This informs us of the importance of interferons for the clearance of virus infections. Treatment with interferon will override the inhibitory effects of the virus." Dr. Fish is Director, Arthritis & Autoimmunity Research Centre; Canada Research Chair in Women's Health & Immunobiology; Senior Scientist, Division of Advanced Diagnostics, Toronto General Research Institute, University Health Network (UHN); and Associate Chair, International Collaborations & Initiatives and Professor, Department of Immunology, University of Toronto.

FirstHealth of Carolinas Joins Mayo Clinic in Convalescent Plasma Program to Treat COVID-19

FirstHealth of the Carolinas (https://www.firsthealth.org/) has joined the convalescent plasma expanded access program (EAP) at the Mayo Clinic to provide plasma transfusion treatment for hospitalized patients with severe or life-threatening COVID-19. Patients who have recovered from COVID-19 are encouraged to donate convalescent plasma through OneBlood (https://www.oneblood.org/). The plasma is then processed and tested for antibodies that help fight against the virus. “A very old treatment is taking part of the blood of someone who recovered from a disease, someone who has the necessary antibodies to fight it, and giving it to a person with the disease,” said Gretchen Shaughnessy Arnoczy, MD, an infectious diseases physician with FirstHealth of the Carolinas. “Convalescent plasma is a promising treatment because it’s worked for other diseases.” To be eligible for donation, individuals must have recovered from coronavirus, become completely free of symptoms for 14 days, and test negative for the virus. Once all criteria are met, recovered patients can register to donate at OneBlood.org. FirstHealth has performed its first successful plasma transfusion, and Dr. Arnoczy said more will occur as long as availability allows. The Mayo Clinic program includes protocols and regulatory assistance, but does not supply the plasma. Sites are encouraged to establish local channels and to work with blood banks to identify and recruit donors. “We want to have a more robust pipeline of plasma available to us,” Dr. Arnoczy said. “We really want to encourage people who have recovered from COVID to go on the OneBlood website and register. That will help us have more supply, so we can use it in more patients.” After donation, plasma, the liquid portion of the blood, is separated and tested. On average, processing takes about 24 hours.

UK Researchers Develop Small Molecules That May Inhibit Cytokine Storm in COVID-19

A COVID-19 treatment, which could potentially also help protect cancer and organ transplant patients, is being developed at the University of Greenwich in the UK, according to a May 15, 2020 release from the University. University researchers have identified and developed compounds that can inhibit the multiple cytokine proteins that can cause death by respiratory collapse, following COVID-19 infection. Michael Leach (https://www.gre.ac.uk/people/rep/faculty-of-engineering-and-science/mike... ), PhD, has developed the compounds, known as UoG-alpha and UoG-beta. He says: “A major force that kills people who have COVID-19 is what’s known as the ‘cytokine storm.’ This is essentially a massive overload of the body’s immune system in response to the virus. Vaccination is what the government is suggesting for the future as being key to how we live ‘normally.’ That makes sense of course, but, as a complement, we need a drug therapy that can be used by someone with COVID symptoms before their ‘perfect storm.’ This would mean they don’t need to go to the hospital, although it could be used there as well. What we have identified and developed at the University are compounds that can control cytokines, which we know are contributing to COVID-19 deaths. We have been working with these small molecules for many years and they have shown themselves to control multiple target proteins linked with many disorders, such as sepsis, cancer, and various inflammatory problems. I believe a controllable drug therapy, able to prevent our immune system from disabling the body’s lung function during a cytokine storm, is what is needed.

CytoDyn Offers No-Cost Exploratory Laboratory Testing for Kawasaki-Like Childhood Inflammatory Disease Associated with COVID-19; CytoDyn Has Monoclonal Antibody Drug (Leronlimab) in Clinical Trials for Treatment of COVID-19

On May 15, 2020, CytoDyn Inc. (OTC.QB: CYDY) (http://www.cytodyn.com), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced that it is offering comprehensive cytokine profiling (including RANTES levels) (RANTES/CCL5: https://en.wikipedia.org/wiki/CCL5) through its diagnostic partner company, IncellDx (https://incelldx.com/), to help physicians understand the pathogenesis of Childhood Inflammatory Disease Related to COVID-19. These laboratory tests are exploratory in nature and not intended for clinical decision-making. Recent reports in parts of the U.S. and Europe suggest a rare and potentially fatal inflammatory disease linked to the novel coronavirus is afflicting a small number of children. The condition resembles a rare childhood illness called Kawasaki disease, which has similar signs and symptoms and can lead to enlargement of blood vessels that, in severe forms, may cause heart damage. The New York State Department of Health is currently investigating 110 reported cases and 3 deaths in children--predominantly school-aged--experiencing symptoms similar to Kawasaki disease and toxic shock-like syndrome, possibly due to COVID-19.