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Archive - Jul 2020

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July 16th

ISEV 2020 Virtual Annual Meeting (July 20-22) Will Be Covered by BioQuick News

The International Society for Extracellular Vesicles (ISEV) Annual Meeting (ISEV 2020), Including Exosomes, is now VIRTUAL (July 20-22); and will be featuring over 600 discussions (Plenary Addresses, Panel Sessions, Featured Abstracts, Oral Abstract Talks, Poster Chats, & Education Sessions), including both live and on-demand presentations. The meeting program can viewed here (https://www.isev.org/mpage/2020Program) and registration can be done here (https://www.isev.org/mpage/2020Registration). As Philip Askenase, MD, eminent Yale Medical School Professor and 30-Year Chief of Allergy & Immunology at Yale, has said, "Exosomes are a sensational biological discovery and they seem to be involved in nearly all biological and clinical processes.” Please consider attending the virtual ISEV 2020 meeting to learn more about these fascinating and immensely important tiny particles. And if you can’t make the live sessions July 20-22, be aware that all meeting presentations and other materials will be available to all registrants until September 21. BioQuick News (http://www.bioquicknews.com) is covering the ISEV 2020 Virtual Annual Meeting and will be posting articles throughout the meeting, and also afterwards. BioQuick News is dedicated to the timely reporting of key life science & medicine advances from around the globe. Headquartered in Madison, Wisconsin, USA, BioQuick News is a wholly independent publication and presently has readers in over 160 countries. BioQuick also has a Japanese-language edition. BioQuick has received numerous awards for publishing excellence and was recently ranked among the “Best Biology Blogs on the Planet.” BioQuick currently offers over 5,500 fully accessible articles on major life science/medicine advances (including >300 stories on exosomes/EVs).

July 16th

UT Research Effort Reveals Co-Crystal Structure of Inhibitor Bound to Dengue Viral Capsid Protein; Structural Information Opens Avenues to Rational Design of Inhibitors for Antiviral Development

A multidisciplinary team from The University of Texas Medical Branch (UTMB) at Galveston has uncovered a new mechanism for designing antiviral drugs for the dengue virus. The results of the new study were published online on July 15, 2020 in PNAS. The article is titled “A Cocrystal Structure of Dengue Capsid Protein in Complex of Inhibitor.” Dengue virus is a very important mosquito-transmitted viral pathogen, causing 390 million human infections each year. Dengue is common in more than 100 countries and forty percent of the world's population is at risk of infection. When someone becomes ill with dengue, symptoms that can range from mild to severe may include fever, nausea/vomiting, rash, and muscle/bone/joint aches. Despite this, there are no clinically approved drugs currently available to people who become infected. In this study, the UTMB team has solved the co-crystal structure of the dengue capsid protein, which forms the interior of the virus, in complex with an inhibitor. The co-crystal structure has provided atomic details of how the inhibitor binds the capsid protein and blocks its normal function, leading to the inhibition of viral infection. The structural information has opened new avenues to rationally design inhibitors for antiviral development. "There are four types of dengue virus, all of which can cause epidemics and disease in humans. The current inhibitor does not inhibit all types of dengue virus. Our co-crystal structure explains why this is the case," said Pei-Yong Shi, PhD, the I.H. Kempner Professor of Human Genetics at UTMB. "Using this new information, we will be able to design new drugs that can inhibit all types of dengue virus. In addition, the structural information will also enable us to make compounds with improved potency and drug-like properties."

July 15th

Evox Therapeutics Expands Existing Exosome Patent Portfolio with Further Grant Covering Exosomes for RNA Therapeutics

On July 15, 2020, Evox Therapeutics Ltd, a leading exosome therapeutics company, is pleased to announce that the company has been granted a key patent by the United States Patent and Trademark Office (USPTO). This newly issued patent adds to the expanding foundational patent estate held by Evox and further reinforces the company's position within the field of exosome-mediated RNA drug delivery. The recently issued US patent (U.S. Patent 10,704,047) provides broad coverage for pharmaceutical compositions comprising exosomes containing nucleic acid-based therapeutics, such as RNAi agents and antisense oligonucleotides, which have been loaded by electroporation. Per Lundin, PhD, Chief Operating Officer of Evox, commented: "We are very pleased to have been granted another foundational patent, reflecting our scientific and IP leadership in the exosome therapeutics space. This is another significant development that gives Evox dominant coverage in exosome-mediated RNA delivery, as well as key steps in the manufacturing process." Antonin de Fougerolles, PhD, Chief Executive Officer of Evox, added: "Over the past decade, Evox has built an unrivaled global patent estate with broad and deep coverage of the key applications of exosome therapeutics. This recent grant represents a great addition of our IP position and further reinforces Evox's leading position as the partner of choice in the field of exosome therapeutics." Evox Therapeutics is a privately held, Oxford UK-based biotechnology company focused on harnessing and engineering the natural delivery capabilities of extracellular vesicles, known as exosomes, to develop an entirely new class of therapeutics.

New Study Illuminates Brain Circuitry Involved In Dysfunctional Social, Repetitive, and Inflexible Behaviors Characteristic of Autism Spectrum Disorders (ASD); Increased Understanding Gives Hope of Perhaps Eventually Treating Aberrant Behaviors in ASD

A team led by University of Texas Southwestern (UTSW) researchers has identified brain circuitry that plays a key role in the dysfunctional social, repetitive, and inflexible behavioral differences that characterize autism spectrum disorders (ASD). The findings, published online on July 13, 2020 in Nature Neuroscience (https://www.nature.com/articles/s41593-020-0665-z), could lead to new therapies for these relatively prevalent disorders. The article is titled “Regulation of Autism-Relevant Behaviors by Cerebellar–Prefrontal Cortical Circuits.” The Centers for Disease Control and Prevention (CDC) estimate that approximately 1 in 54 children in the United States have ASD, a broad range of neurodevelopmental conditions thought to be caused by a combination of genetic and environmental factors. Although researchers have identified some key genes and pathways that contribute to ASD, the underlying biology of these disorders remains poorly understood, says Peter Tsai (https://profiles.utsouthwestern.edu/profile/153860/peter-tsai.html), MD, PhD, Assistant Professor in the Departments of Neurology and Neurotherapeutics, Neuroscience, Pediatrics, and Psychiatry at UTSW Medical Center and a member of the Peter O’Donnell Jr. Brain Institute (https://utswmed.org/odonnell/). However, Dr. Tsai explains, one key brain region that’s been implicated in ASD dysfunction is the cerebellum, part of the hindbrain in vertebrates that holds about three-quarters of all the neurons in the body and has traditionally been linked with motor control. Recent studies by Dr. Tsai and his colleagues have demonstrated that inhibiting activity in a region of the cerebellum known as Rcrus1 can cause altered social and repetitive/inflexible behaviors reminiscent of ASD in mice.

International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting, Including Exosomes, July 20-22: Plenary Speakers, Panel Sessions, Featured Abstracts, Oral Abstracts, Poster Chats, & Educational Sessions; FOCUS: 19 MEETING SPONSORS

The International Society for ExtracellularVesicles (ISEV) AnnualMeeting (ISEV2020), Including Exosomes, Is Now VIRTUAL (July 20-22); and will feature over 600 Discussions (Plenary Addresses, Panel Sessions, Featured Abstracts, Oral Abstract Talks, Poster Chats, & Education Sessions). The program can viewed here (https://www.isev.org/mpage/2020Program) and registration can be done here (https://www.isev.org/mpage/2020Registration). As Philip Askenase, MD, eminent Yale Medical School Professor and 30-Year Chief of Allergy & Immunology there, has said, “Exosomes are a sensational biological discovery and they seem to be involved in nearly all biological and clinical processes.” This year’s ISEV annual virtual meeting is being sponsored by a total of 19 companies (https://www.isev.org/mpage/2020Sponsorship) that are keenly interested in the potential of EVs for a wide variety of applications. A list of the ISEV 2020 sponsoring companies, including links to each company’s web site is provided below. Please note that BioQuick News, which will be covering the ISEV 2020 virtual annual meeting, is one of the Bronze Sponsors of this important meeting. PLATINUM SPONSORS: FujiFilm (https://www.fujifilm.com/), Izon (https://izon.com/), NanoFCM (https://www.nanofcm.com/), NanoView Biosciences (https://www.nanoviewbio.com/), Particle Metrix (https://www.particle-metrix.de/en/particle-metrix), and RoosterBio (https://www.roosterbio.com/). GOLD SPONSORS: Beckman Coulter (https://www.beckman.com/), Luminex (https://www.luminexcorp.com/), Malvern Panalytical (https://www.malvernpanalytical.com/en/), Myriade (http://www.myriadelab.com/en/), and Streck (https://www.streck.com/).

BRCA2: An Unexpected Role for This Tumor Suppressor Gene Discovered; Mutations in BRCA2 Impair Alignment of Chromosomes at the Metaphase Plate & May Be Associated with Chromosome Number Aberrations Often Seen in BRCA2-Related Cancers

The BRCA2 protein, produced by the expression of the tumor suppressor gene BRCA2, plays an important role in DNA repair by homologous recombination, which takes place at early phases of the cell cycle. A team from Institut Curie, in collaboration with a group of CEA, revealed an additional role of BRCA2 in the alignment of chromosomes during mitosis (cell division), with significant consequences on chromosome stability. Published in Nature Communications, these results could explain certain chromosomal aberrations observed in BRCA2-mutated tumors. The “Genome Instability and Cancer Predisposition” Team (https://science.institut-curie.org/research/biology-chemistry-of-radiati...) led by Aura Carreira (photo), PhD, in the “Genome integrity, RNA and Cancer” Unit (CNRS/Paris-Saclay University/Institut Curie) is working on the role of BRCA2 in maintaining genome integrity. It was already known that BRCA2 operates in DNA repair by homologous recombination, the DNA duplication phase of the cell cycle. In addition, it was also known that a mutation in the BRCA2 gene predisposes to breast and ovarian cancer. In collaboration with the group of Sophie Zinn-Justin, PhD, at the CEA, Dr. Carreira’s team found an additional and unexpected role of BRCA2 in mitosis, which seems uncoupled to its function in DNA repair. Using a combination of biophysics, biochemistry, cell biology, and genetics tools, these researchers showed that the alignment of chromosomes at the metaphase plate depends on the phosphorylation of BRCA2 by the protein kinase PLK1 (polo-like kinase 1). Importantly, they found that certain BRCA2 variants identified in breast cancer patients were associated with this function during mitosis being altered.

July 14th

Moderna Announces Publication in NEJM of Interim Results from Phase 1 Study of Its mRNA Vaccine (mRNA-1273) Against COVID-19; Neutralizing Antibody Titers Observed in 100% of Evaluated Participants; Phase 3 Study to Begin July 27

On July 14, 2020, Moderna, Inc. (Nasdaq:MRNA), a clinical-stage biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines to create a new generation of transformative medicines for patients, announced the publication of an interim analysis of the open-label Phase 1 study of mRNA-1273, its vaccine candidate against COVID-19, in The New England Journal of Medicine (https://www.nejm.org/doi/full/10.1056/NEJMoa2022483?query=featured_home). The open-acccess article, published online today (July 14, 2020) is titled “An mRNA Vaccine Against SARS-CoV-2--Preliminary Report.” This interim analysis evaluated a two-dose vaccination schedule of mRNA-1273 given 28 days apart across three dose levels (25, 100, 250 µg) in 45 healthy adult participants ages 18-55 years, and reports results through Day 57. Results from participants in the initial dose cohorts who received both vaccinations and were evaluated at pre-specified timepoints reaffirm the positive interim data assessment announced (https://investors.modernatx.com/news-releases/news-release-details/moder...) on May 18th and show that mRNA-1273 induced rapid and strong immune responses against SARS-CoV-2. The study was led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). mRNA-1273 was generally safe and well-tolerated, with no serious adverse events (SAEs) reported through Day 57. Adverse events (AEs) were generally transient and mild to moderate in severity. The most notable adverse events were seen at the 250 µg dose level, with three of those 14 participants (21%) reporting one or more severe events.

Extracellular Vesicles Displaying ACE2 Can Prevent Infection by SARS-CoV-2 Spike-Protein-Pseudotyped Lenti Virus; ACE2-EVs Are Up to 1500X As Effective As Soluble ACE2; Infection Prevention Further Enhanced by Inclusion of TMPRRS2 in EV Surface

In a non-final, non-peer-reviewed, pre-print* article, published online on July 8, 2020 on the pre-print portal bioRxiv,* researchers in Paris, France, have shown that extracellular vesicles (EVs) bearing the surface receptor ACE2 (angiotensin-converting enzyme 2), to which the spike (S) protein of SARS-CoV-2 virus binds when infecting human cells, may serve as decoys to the invading virus because such EVs effectively prevent infection of ACE2-bearing cells by a SARS-Co-V2 S-protein-pseudotyped lenti virus in vitro. The authors note that SARS-CoV-2 entry is mediated in COVID-19 by binding of the viral S protein to the host cell surface receptor ACE2 and subsequent priming by host cell TMPRRS2 (transmembrane protease, serine 2) that allows membrane fusion and viral entry to the cell. The researchers said that the reduction of infectivity correlates positively with the level of EV ACE2 This reduction in infectivity is 500X to 1500X more efficient than is achieved with soluble ACE2, and is further enhanced by inclusion of TMPRRS2 in the EV surface. The researchers conclude that ACE2-EVs represent a potential versatile therapeutic tool to block, not only SARS-CoV-2 infection, but also infections by other coronaviruses that use ACE2 for host cell entry. The open-access article on the bioRxiv portal is titled “Extracellular Vesicles Containing ACE2 Efficiently Prevent Infection by SARS-Cov-2 Spike Protein-Containing Virus” (https://www.biorxiv.org/content/10.1101/2020.07.08.193672v1?fbclid=IwAR0...). The co-senior and co-corresponding authors of this open-access article are Mercedes Tkach, PhD; Clotilde Thery, PhD; and Lorena Martin-Jaular, PhD, each of INSERM U932, Institut Curie Centre de Recerche, PSL Research University, Paris, France.

Scientists Identify Oncogene (AVIL) That Drives Glioblastoma; Discovery Offers Promising New Treatment Target for Possible Treatment of a Cancer That Is Always Fatal

Scientists have identified an oncogene (a cancer-causing gene) responsible for glioblastoma, the deadliest brain tumor. The discovery offers a promising new treatment target for a cancer that is always fatal. The researchers say the oncogene is essential to the survival of the cancer cells. Without it, the cancer cells die. Scientists have already developed many targeted therapies for other cancers with a similar "oncogene addiction." "Glioblastoma is one of the deadliest cancers. Unfortunately, there is no effective treatment option for the disease. The current standard option, radiation plus temozolomide, which displayed a 2.5-month better survival rate, was hailed as a great success. Clearly, better understanding and new therapeutic targets are urgently needed," said researcher Hui Li, PhD, of the University of Virginia (UVA) School of Medicine and the UVA Cancer Center. "The novel oncogene we discovered promises to be an Achilles' heel of glioblastoma, with its specific targeting potentially an effective approach for the treatment of the disease." Oncogenes are naturally occurring genes that spiral out of control and cause cancer. The oncogene that Dr. Li and his colleagues identified, avilllin (AVIL), normally helps cells maintain their size and shape. But the gene can be shifted into overdrive by a variety of factors, the researchers found. This causes cancer cells to form and spread. Blocking the gene's activity completely destroyed glioblastoma cells in lab mice but had no effect on healthy cells. This suggests targeting the gene could be an effective treatment option.

A Balancing Act Between Immunity and Longevity; Mutation in Splicing Factor RNP-6 Inhibits Immune Response in C. elegans, But Increases Lifespan, Barring Infection; RNP-6 Human Orthologue, Splicing Factor PUF60, May Also Be Involved in Immunity & Lifespan

As we age, the immune system gradually becomes impaired. One aspect of thisA Balancing Act Between Immunity and Longevity; Mutation in Splicing Factor RNP-6 Inhibits Immune Response in C. elegans, But Increases Lifespan, Barring Infection; RNP-6 Human Orthologue Splicing Factor PUF60 May Also Be Involved in Immunity & Lifespan impairment is chronic inflammation in the elderly, which means that the immune system is constantly active and sends out inflammatory substances. Such chronic inflammation is associated with multiple age-related diseases including arthritis and Alzheimer's disease, and impaired immune responses to infection. One of the questions in aging research is whether chronic inflammation is a cause of aging, or a consequence of the aging process itself? Scientists in the laboratory of Adam Antebi, PhD, Director of the Max Planck Institute for Biology of Aging in Cologne, Germany, have found evidence suggesting that increased inflammation causes the aging process to speed up, and that there is a fine balance between maintaining immune system function and longevity. From their work in the tiny roundworm, Caenorhabditis elegans, the scientists discovered a mutation in an evolutionarily conserved gene [the RNP-6 (ribonucleoprotein 6) gene in C. elegans, whose orthologous gene in humans is called PUF60 (poly U binding splicing factor 60)], which made the worms long-lived, but, at the same time, dampened their immune response. Worms with this mutation lived about 20% longer than normal worms, but when they were infected with certain bacteria, they succumbed more quickly to the infection. This suggests that an overactive immune system also has a price: it shortens life span. Conversely, a less active immune system pays off in a longer life span--as long as the animal does not die from an infection.