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October 10th, 2018

NanoView Completes $10 Million Series B Financing Funding to Support Commercialization of ExoView™ System, NanoView’s Complete Exosome Detection and Characterization Platform; Financing Led by Northpond Ventures

On October 10, 2018, NanoView Biosciences, an emerging leader in the field of exosome detection and characterization, announced the closing of a $10 million Series B financing led by Northpond Ventures. Existing investors, including Sands Capital Ventures and PBM Capital Group, participated in the financing round. Proceeds will be used to complete development of the ExoView system, NanoView’s complete exosome detection and characterization platform, and to prepare the product for commercial launch. “Northpond Ventures really understands the need for more accurate, efficient approaches to characterizing exosomes and we are excited to have them join our current investors,” said Jerry Williamson, Chief Executive Officer of NanoView. “With these funds we are well positioned to complete the development of the first applications of our ExoView system. We plan to launch this platform for research markets in early 2019 and then expand into developing tools for clinical markets in the future.” Exosomes are nanoscale extracellular vesicles secreted by most cell types; they represent a communication system between cells. A growing body of research supports the potential of exosomes to diagnose, monitor, and even treat a broad range of diseases. Most currently available methods for analyzing exosomes are cumbersome, expensive, and require large sample volumes that are not readily available. According to NanoView, the ExoView system is an innovative instrument and consumables platform that efficiently and accurately enables complete detection and characterization of extracellular vesicles, including exosomes.

October 10th

Anti-Psychotic Drug May Be Effective Against Triple-Negative Breast Cancer

A commonly used anti-psychotic drug could also be effective against triple-negative breast cancer, the form of the disease that is most difficult to treat, new research has found. The study, led by the University of Bradford in the UK, also showed that the drug, pimozide, has the potential to treat the most common type of lung cancer. Anti-psychotic drugs are known to have anti-cancer properties, with some studies, albeit inconclusive, showing a reduced incidence of cancer amongst people with schizophrenia. The new research, published online on October 9, 2018 in Oncotarget, is the first to identify how one of these drugs acts against triple-negative breast cancer, with the potential to be the first targeted treatment for the disease. Lead researcher, Professor Mohamed El-Tanani (photo) from the University of Bradford, said: "Triple-negative breast cancer has lower survival rates and increased risk of recurrence. It is the only type of breast cancer for which only limited targeted treatments are available. Our research has shown that pimozide could potentially fill this gap. And because this drug is already in clinical use, it could move quickly into clinical trials." The researchers, from the University of Bradford, Queen's University Belfast (Northern Ireland), and the University of Salamanca (Spain), tested pimozide in the laboratory on triple-negative breast cancer cells, non-small cell lung cancer cells, and normal breast cells. They found that, at the highest dosage used, up to 90 per cent of the cancer cells died following treatment with the drug, compared with only 5 per cent of the normal cells. The researchers then tested the drug on mice implanted with triple-negative breast cancer.

Specific Gene Types Driving Higher Frequency of Myeloma Diagnosis in African-Americans Identified By Mayo Clinic Researchers; DNA Sequencing Used to More Accurately Determine Racial Ancestry; Findings May Aid Insight into Best Forms of Therapy

Researchers at the Mayo Clinic in Rochester, Minnesota, have identified three specific gene types that account for a known two-to-three-fold increase in myeloma diagnoses among African-Americans. Researchers also demonstrated the ability to study race and racial admixture more accurately using DNA analysis. The findings were published online on October 10, 2018 in Blood Cancer Journal. The open-access article is titled “Differences in Genomic Abnormalities Among African Individuals with Monoclonal Gammopathies Using Calculated Ancestry.” "Myeloma is a serious blood cancer that occurs two to three times more often in African-Americans than Caucasians," says Vincent Rajkumar(photo), MD. a hematologist at the Mayo Clinic and senior author of the study. "We sought to identifying the mechanisms of this health disparity to help us better understand why myeloma occurs in the first place and provide insight into the best forms of therapy." Dr. Rajkumar and his colleagues studied 881 patients of various racial groups. Researchers found that the higher risk of myeloma known to occur in African-Americans was driven by three specific subtypes of the cancer characterized by the presence of genetic translocations in cancer cells. Translocations are genetic abnormalities in cancer cells caused by the rearrangement of parts between nonhomologous chromosomes. The translocation researchers identified were t(11;14), t(14;16), and (t14;20). "Previous efforts to understand this disparity have relied on self-reported race rather than on genetic ancestry, which may have resulted in bias," explains Dr. Rajkumar. "A major new aspect of this study is that we identified the ancestry of each patient through DNA sequencing, which allowed us to determine ancestry more accurately." Dr.

October 9th

EXOSOME NEWS: Avalon GloboCare Teams with Weill Cornell Medicine to Co-Develop Standardization of cGMP-Grade Exosome Isolation and Application of Tissue-Specific Exosomes

On October 9, 2018, Avalon GloboCare Corp. (OTCQB: AVCO), a leading global developer of cell-based technologies and therapeutics, headquartered in New Jersey, USA, announced that Weill Cornell Medicine has selected its subsidiary Genexosome Technologies’ proprietary exosome isolation system as a key component in the world’s first standardization processing of cGMP-grade exosomes for clinical studies. This co-development program is led by Yen-Michael Hsu, MD, PhD, Director of cGMP Cellular Therapy Facility and Laboratory for Advanced Cellular Engineering at Weill Cornell. This co-development program will focus on two main objectives: (1) standardization of cGMP-grade exosome isolation from human endothelial cells, essential for vascular health and organ regeneration; and (2) identification and isolation of tissue-specific exosomes for liquid biopsy and clinical use. A material transfer agreement will accompany this announcement to facilitate and authorize the use of GenExosome’s isolation system by Weill Cornell. “Identification and isolation of tissue-specific exosomes is considered by many as the “Holy Grail” in this area. This co-development and standardization initiative with Weill Cornell has further enhanced the global recognition, intellectual property, as well as our leading role in this industry sector,” stated Yu Zhou, MD, PhD, Founder and Co-CEO of GenExosome Technologies, Inc. "This strategic co-development endeavor will synergize Genexosome Technologies’ top-rated isolation platform with Weill Cornell’s world-class cGMP cellular therapy/cell-derived product processing facility to accelerate innovative exosome technology development, as well as standardization in clinical-grade exosome bio-production process,” stated David Jin, MD, PhD, CEO and President of Avalon GloboCare Corp.

Two Genes Responsible for Remarkable Difference in Flower Color of Nearby Snapdragons Identified; Islands of Divergence Established by Gene Flow & Multiple Selective Sweeps; Bee Pollination a Key Factor

Snapdragons are charming tall plants that flower in a range of bright colors. In Spain, where snapdragons grow wild, these flower colors show a remarkable pattern: When driving up a road from Barcelona to the Pyrenees, snapdragons of the species Antirrhinum majus bloom in magenta at the beginning of the road, before a population of yellow flowering snapdragons takes over - separated by just a two kilometer c long stretch in which flower colors mix. Such hybrid zones of snapdragons are quite infrequent; only a few others are known. But why don't the snapdragons mix, with yellow and magenta flowers growing together over a wide area? Dr. Nick Barton at the Institute of Science and Technology Austria (IST Austria), together with Dr. David Field, previously a postdoc in Dr. Barton's group and now Assistant Professor at the University of Vienna, collaborated with molecular geneticists at the John Innes Center in Norwich, UK, to investigate the causes of this pattern. In an article published online on October 8, 2018 in PNAS, the scientists report that they identified the genes responsible for flower color difference from DNA sequence data. The open-access article is titled “Selection and Gene Flow Shape Genomic Islands That Control Floral Guides.” "DNA sequencing is becoming cheaper and cheaper. But analyzing sequence data and interpreting the patterns seen is very hard,” Dr. Barton explains. “In this study, we used sequence data from Antirrhinum plants to locate the individual genes that are responsible for the difference in flower color across the hybrid zone." The researchers compared the genome sequences of 50 snapdragons of each color, and measured how much the sequences diverged between magenta and yellow snapdragon populations.

Phenylketonuria Cured in Mouse Model by Adaptation of CRISPR/Cas9 Gene Editing—60% Gene Correction Rate Achieved Employing Base Editor Cytidine Deaminase

Parents of newborns may be familiar with the metabolic disorder phenylketonuria: in Switzerland, all newborn babies are screened for this genetic disease. If a baby is found to have phenylketonuria, he or she requires a special diet so that the amino acid phenylalanine does not accumulate in the body. Excess phenylalanine delays mental and motor development. If left untreated, the children may suffer massive mental disability. The cause of this metabolic disorder is a mutation in a gene that provides the blueprint for the enzyme phenylalanine hydroxylase (Pah). This enzyme, which is produced by the cells of the liver, metabolizes phenylalanine. The disorder is referred to as "autosomal recessive"--the child develops the disease if he or she inherits one mutated Pah gene from the mother and one from the father. There has been no cure for this disorder to date. A team of researchers led by ETH Zurich professor Gerald Schwank has now taken advantage of a method to correct both mutated genes in the liver cells and thus heal the disease. (Editor’s Note: ETH Zurich is a science, technology, engineering, and mathematics university in the city of Zürich, Switzerland.) Dr. Schwank’s team has succeeded, at least in mice. With the help of a CRISPR/Cas9 system extended by one enzyme, the researchers changed the sequence of the DNA building blocks for the Pah corresponding gene in adult mice. The mouse liver cells were subsequently able to produce functioning Pah enzymes, and the mice were healed. The work was reported online on October 8, 2018 in Nature Medicine. The article is titled “Treatment of a Metabolic Liver Disease by In Vivo Genome Base Editing in Adult Mice.” Following are more details on the work.

October 5th

New Nanopore System Can Detect Multiple Small Molecules in Nanoliter of Biological Fluids Quickly and Simultaneously; May Lay Foundation for Disruptive New Technology for Medical Diagnostics

University of Groningen (Netherlands) scientists, led by Associate Professor of Chemical Biology Giovanni Maglia, have designed a nanopore system that is capable of measuring different metabolites simultaneously in a variety of biological fluids, all in a matter of seconds. The electrical output signal is easily integrated into electronic devices for home diagnostics. The results were published online on October 5, 2018 in Nature Communications. The open-access article is titled “Direct Electrical Quantification of Glucose and Asparagine from Bodily Fluids Using Nanopores.” Measuring many metabolites or drugs in the body is complicated and time-consuming, and real-time monitoring is not usually possible. The ionic currents that pass through individual nanopores are emerging as a promising alternative to standard biochemical analysis. Nanopores are already integrated into portable devices to determine DNA sequences. “But it is basically impossible to use these nanopores to specifically identify small molecules in a complex biological sample,” says Dr. Maglia. A year ago, Dr. Maglia and colleagues demonstrated how to use nanopores to identify the “fingerprints” of proteins and peptides, and even to distinguish polypeptides that differ by one amino acid (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715100/). Now, he has adapted this system to identify small molecules in biological fluids. To do so, he used a larger cylindrical-shaped nanopore to which he added substrate-binding proteins. “Bacteria make hundreds of these proteins to bind substrates in order to transport them into the cells. These proteins have specificities that have evolved over billions of years.” Dr. Maglia adapts the binding proteins to fit inside the nanopore. If a protein then binds to its substrate, it changes its conformation.

2018 Chemistry Nobel Awarded for Directed Evolution of Enzymes & Phage Display

On October 3, 2018, The Royal Swedish Academy of Sciences announced that it had decided to award the Nobel Prize in Chemistry 2018 with one half to Dr. Frances H. Arnold (photo), California Institute of Technology, Pasadena, USA, “for the directed evolution of enzymes,” and the other half jointly to George P. Smith, University of Missouri, Columbia, USA, and Sir Gregory P. Winter, MRC Laboratory of Molecular Biology, Cambridge, UK, “for the phage display of peptides and antibodies.” The power of evolution is revealed through the diversity of life. The 2018 Nobel Laureates in Chemistry have taken control of evolution and used it for purposes that bring great benefit to humankind. Enzymes produced through directed evolution are used to manufacture everything from biofuels to pharmaceuticals. Antibodies evolved using a method called phage display can combat autoimmune diseases and, in some cases, cure metastatic cancer. Since the first seeds of life arose approximately 3.7 billion years ago, almost every crevice on Earth has filled with different organisms. Life has spread to hot springs, deep oceans and dry deserts, all because evolution has solved a number of chemical problems. Life’s chemical tools – proteins – have been optimized, changed and renewed, creating incredible diversity. This year’s Nobel Laureates in Chemistry have been inspired by the power of evolution and used the same principles – genetic change and selection – to develop proteins that solve mankind’s chemical problems. One half of this year’s Nobel Prize in Chemistry is awarded to Dr. Arnold. In 1993, she conducted the first directed evolution of enzymes. Since then, she has refined the methods that are now routinely used to develop new catalysts. The uses of Dr.

October 2nd

Natural Product (Fisetin) Found to Extend Healthspan in Animal Model; Mass Spec Technique Shows Effects on Specific Subsets of Cells

Previous research published earlier this year in Nature Medicine (https://www.nature.com/articles/s41591-018-0092-9) involving University of Minnesota Medical School faculty Dr. Paul D. Robbins and Dr. Laura J. Niedernhofer and Mayo Clinic investigators Dr. James L. Kirkland and Dr. Tamara Tchkonia, showed it was possible to reduce the burden of damaged cells, termed senescent cells, and extend lifespan and improve health, even when treatment was initiated late in life. They now have shown that treatment of aged mice with the natural product fisetin (image), found in many fruits and vegetables, also has significant positive effects on health and lifespan. As people age, they accumulate damaged cells. When the cells get to a certain level of damage they go through an aging process of their own, called cellular senescence. The cells also release inflammatory factors that tell the immune system to clear those damaged cells. A younger person's immune system is healthy and is able to clear the damaged cells. But, as people age, these damaged cells aren't cleared as effectively. Thus, they begin to accumulate, cause low level inflammation, and release enzymes that can degrade tissue. Dr. Robbins and fellow researchers found that a natural product, called fisetin, reduces the level of these damaged cells in the body. They found this by treating mice towards the end of life with this compound and seeing improvement in health and lifespan. The open-access article, "Fisetin Is a Senotherapeutic That Extends Health and Lifespan," was published on September 29, 2018 in EBioMedicine. "These results suggest that we can extend the period of health, termed healthspan, even towards the end of life," said Dr. Robbins. "But there are still many questions to address, including the right dosage, for example."

October 2nd

Miniature Magnetic Swimming Devices May Revolutionize Diagnostics and Drug Delivery; Devices Can Be Made on Industrial Scale

Scientists have created miniature magnetic swimming devices - which mimic the appearance of sperm cells - that could revolutionize disease treatment by ferrying drugs to specific areas of the body. The devices, which measure as small as one millimeter long, consist of a magnetic head and flexible tail that allows them to “swim” to a specific location when activated by a magnetic field. Researchers at the University of Exeter in the UK, who designed the devices and magnetic control mechanism, have also created a mathematical model that allows them to predict the devices’ behavior in different environments, such as microfluidic channels or complex liquids. The researchers believe that the devices could be used to deliver drugs to specific areas of the body, thus potentially dramatically improving treatment time and success. The scientists also believe that the devices could revolutionize the wider field of microfluidics, which focuses on moving liquids through extremely narrow channels. The team’s research is currently focused on implementing microscopic prototypes and the researchers have already successfully demonstrated swimmers comparable to the size of red blood cells. The research was published recently in the Physics of Fluids journal. Professor Feodor Ogrin, principal investigator at the University of Exeter said: "Developing this technology could radically change the way we do medicine. The swimmers could one day be used to direct drugs to the right areas of the body by swimming through blood vessels. We also envisage microscopic versions of the device being used on 'lab-on-a-chip' technology, where complex procedures normally conducted in a laboratory, such as diagnosing disease, are conducted on a simple chip.