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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.

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.

Biocon Describes Clinical Study Enabling Approval of Itolizumab for COVID-19 in India; Novel Anti-CD6 Monoclonal Antibody Reduces Release of Pro-Inflammatory Cytokines, Controls “Cytokine Storm,” & Reduces COVID-19 Mortality

On July 13, 2020, Biocon Ltd. (BSE code: 532523, NSE: BIOCON), an innovation-led global biopharmaceuticals company, headquartered in Bengaluru, Karntaka, India, presented key insights into the results of the pivotal study that demonstrated its novel biologic, itolizumab, significantly reduced mortality in moderate to severe ARDS (acute respiratory distress syndrome) patients hospitalized with COVID-19, in India. This led to the Drug Controller General of India (DCGI) approving this novel biologic therapy for restricted emergency use in India. Kiran Mazumdar-Shaw, Executive Chairperson, Biocon, said: “Itolizumab is a ‘Made in India,’ ‘Innovated in India,’ first-in-class anti-CD6 monoclonal antibody, which has a seven-year proven track record of safety as doctors in India have been prescribing this biologic therapy to treat acute psoriasis. As itolizumab has been approved in India and given that we are in the middle of a medical emergency, the regulator has approved Biocon’s product for emergency use based on compelling data from a pivotal clinical trial involving a cohort of 30 patients. The two-arm, randomized study met both the primary and secondary endpoints, with the Itolizumab arm demonstrating statistically significant advantage over the control arm, culminating in the drug’s approval for restricted emergency use by the DCGI. The study results show that itolizumab’s unique mechanism of action can bring down mortality in moderate to severe ARDS patients due to COVID-19.”

International Society for Extracellular Vesicles (ISEV) Announces 39 Scholarship Winners for ISEV 2020 Virtual Annual Meeting (July 20-22) on Extracellular Vesicles, Including Exosomes

On July 13, 2020, the International Society for Extracellular Vesicles (ISEV) Annual Meeting (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). For past annual meetings, the ISEV has awarded meeting scholarships to outstanding young investigators. This year, in addition to the Young Investigator Scholarship category, ISEV has introduced three new scholarship categories: New Parent Member Scholarship (with children up to 8 years of age); Travel Scholarship for Attendees Working in World Bank Low-Income Countries; and Scholarship for Student Hardship (this category is for students who faced exceptional hardship in their careers to achieve their goals). This year’s 39 scholarship winners are listed below, together with their academic affiliations, and the titles and numbers of their abstracts for the meeting. LINA ANTOUNIANS, The Hospital for Sick Children, Canada, Abstract Title: “Epigenetic Regulation of Fetal Hypoplastic Lungs by Amniotic Fluid Stem Cell Derived Extracellular Vesicles” (OT10.4). ISHARA ATUKORALA (photo), La Trobe University, Australia, Abstract Title: “Ubiquitin E3 Ligase NEDD4 Is a Novel Regulator of Exosome Biogenesis and Secretion” (OT09.1). SOUNAK BAGCHI, Texas Tech University Health Sciences Center, USA, Abstract Title: “Bioengineered Exosomes As Novel Drug Carriers for Targeting HIV-1 Infection in the CNS” (OS29.2).

Gut Microbiota May Provide Clues for Detecting, Preventing, and Treating Type 2 Diabetes (T2D); Reduced Potential of Butyrate Production Noted in Prediabetes or Untreated T2D; Butyrate Produced Mainly by Beneficial Bacteria in Digestion of Dietary Fibers

The individual mix of microorganisms in the human gastrointestinal tract provides vital clues as to how any future incidence of type 2 diabetes can be predicted, prevented and treated. This is demonstrated in a population study led from the University of Gothenburg. That a person’s gut microbiota can contribute to type 2 diabetes has been shown in previous research, led by Fredrik Bäckhed, PhD, Professor of Molecular Medicine at Sahlgrenska Academy, University of Gothenburg in Sweden. The present study, published online on July 10, 2020 in Cell Metabolism (https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30312-0), describes newly discovered clues in the microbiota as to how bacteria may contribute to type 2 diabetes and potentially predict who will develop disease based on an individual’s gut microbiota. The Cell Metabolism article is titled “The Gut Microbiota in Prediabetes and Diabetes: A Population-Based Cross-Sectional Study.” By studying people who have not yet developed type 2 diabetes, the researchers were able to rule out the possibility that the gut microbiota was affected by the disease or its treatment. The majority of previous studies in this field have compared healthy individuals with patients. What has emerged is that in individuals with raised fasting blood glucose levels or reduced glucose tolerance, a condition known as prediabetes, as well as in people with untreated type 2 diabetes, the gut microbiota is changed.

International Society for Extracellular Vesicles (ISEV) 2020 Virtual Annual Meeting, Including Exosomes, July 20-22: Plenary Speakers, Panel Sessions, Featured Abstracts, Oral Abstract Talks, Poster Chats, & Education Sessions; FOCUS: EDUCATION SESSIONS

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 eminent Yale Medical School Professor and 30-Year Chief of Allergy & Immunology Philip Askenase, MD, has said, “Exosomes are a sensational biologic discovery and they seem to be involved in nearly all biological and clinical processes.” Among its myriad stimulating and timely offerings, the ISEV 2020 virtual meeting will be offering 23 Educational Presentations, featured in 6 different sessions during the 3-day meeting. These sessions are intended to convey significant background information on the ever-widening impact of extracellular vesicles (EVs), including exosomes, on virtually all aspects of biology and medicine The 23 10-minute educational presentations will be delivered by world leaders in their fields. Below is an outline of the schedule for the Education Sessions, with descriptions of the 23 different presentations and backgrounds on the distinguished presenters and session moderators. Each of the six Education Sessions will include a 15-minute Q&A discussion at its end.

EDUCATION SESSION 1 (MONDAY 2:00 PM EDT—2:48 PM EDT)

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