Category Archives: Gene Medicine

PLEASANTON, Calif., Sept. 15, 2020 (GLOBE NEWSWIRE) --10x Genomics (Nasdaq: TXG) today announced it has begun shipping its Chromium Single Cell Multiome ATAC + Gene Expression solution to customers, marking the first commercial release of a product capable of simultaneously profiling the epigenome and transcriptome from the same single cell. This multi-omic approach provides customers with the ability to link a cells epigenetic program to its transcriptional output, enabling a better understanding of cell functionality and bypassing the need to infer relationships through computer simulations.

This is one of our most ambitious undertakings at the company, said Ben Hindson, co-founder and Chief Scientific Officer of 10x Genomics. By introducing the first solution that captures ATAC and gene expression simultaneously, researchers can gain even more clarity by combining two already powerful methods to profile biological systems at single cell resolution simultaneously for the first time.

The new solution builds on an array of new products launched by the company this year for both its Chromium platform for single cell analysis as well as its Visium platform for spatial genomics. Early customers already working with Chromium Single Cell Multiome ATAC + Gene Expression include Stanford University School of Medicine, Icahn School of Medicine at Mt. Sinai and Spains Centro Nacional de Anlisis Genmico.

My lab is interested in understanding why some immune cell types fail to fight the cancer, said Dr. Ansuman Satpathy, Assistant Professor of Pathology, Stanford University School of Medicine. We plan to use 10x Genomics' new assay to understand the epigenetic and transcriptional regulation of immune cell dysfunction directly in patient samples, and to use this information to precisely engineer more effective immunotherapies in the future.

Until now, we have relied on computational prediction to match a cell's epigenome to a single-cell gene expression profile, said Dr. Holger Heyn, leader of the single cell genomics team at Spains Centro Nacional de Anlisis Genmico that is working on delineating the dynamics underlying B-cell differentiation and activation. 10x Genomics new multiome assay will allow us to directly measure what before could only be predicted, and offers a new gold standard that will confirm how accurate these predictions had been.

"With this new technology, we can better understand the mechanisms affected by the non-coding risk genetic variation across a wide range of neuropsychiatric diseases, including Alzheimers, Parkinsons, Schizophrenia, bipolar disorder and major depression, along with different severity of neuropathology and clinical symptomatology," added Dr. Panagiotis Roussos, Associate Professor of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai.

By using Chromium Single Cell Multiome ATAC + Gene Expression, researchers can:

Chromium Single Cell Multiome ATAC + Gene Expression is shipping to customers. To learn more, visit https://www.10xgenomics.com/products/single-cell-multiome-atac-plus-gene-expression.

About 10x Genomics10x Genomics is a life science technology company building products to interrogate, understand and master biology to advance human health. The companys integrated solutions include instruments, consumables and software for analyzing biological systems at a resolution and scale that matches the complexity of biology. 10x Genomics products have been adopted by researchers around the world including 97 of the top 100 global research institutions and 19 of the top 20 global pharmaceutical companies, and have been cited in over 1,500 research papers on discoveries ranging from oncology to immunology and neuroscience. The companys patent portfolio comprises more than 775 issued patents and patent applications.

Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements generally can be identified by the use of forward-looking terminology such as may, will, should, expect, plan, anticipate, could, intend, target, project contemplate, believe, estimate, predict, potential or continue or the negatives of these terms or variations of them or similar terminology. These forward-looking statements include statements regarding 10x Genomics, Inc.s partnership activities, which involve risks and uncertainties that could cause 10x Genomics, Inc.s actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on managements current expectations, forecasts, beliefs, assumptions and information currently available to management, and actual outcomes and results could differ materially from these statements due to a number of factors. These and additional risks and uncertainties that could affect 10x Genomics, Inc.s financial and operating results and cause actual results to differ materially from those indicated by the forward-looking statements made in this press release include those discussed under the captions "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" and elsewhere in the documents 10x Genomics, Inc. files with the Securities and Exchange Commission from time to time. The forward-looking statements in this press release are based on information available to 10x Genomics, Inc. as of the date hereof, and 10x Genomics, Inc. disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing 10x Genomics, Inc.s views as of any date subsequent to the date of this press release.

Disclosure Information10x Genomics uses filings with the Securities and Exchange Commission, its website (www.10xgenomics.com), press releases, public conference calls, public webcasts and its social media accounts as means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD.

ContactsMedia:media@10xgenomics.comInvestors:investors@10xgenomics.com

Read the original here:
10x Genomics First to Market With Product to Simultaneously Capture Epigenome and TranscriptomeChromium Single Cell Multiome ATAC + Gene Expression...

Scientists from UBCs faculty of medicine and the Institute of Molecular Biology of the Austrian Academy of Sciences (IMBA) have discovered that the gene, known as JAGN1, plays an important role in antibody production and the bodys ability to mount a defense against pathogens, including viruses.

The findings were published online today in the Journal of Experimental Medicine.

Dr. Josef Penninger

Antibodies play a fundamental role in medicine, and antibody-mediated immune response is the ultimate target in the quest for a vaccine to defeat the current pandemic, says the studys senior author Dr. Josef Penninger, a professor in the department of medical genetics and director of the Life Sciences Institute at UBC and a researcher at IMBA.

As part of their investigation, Dr. Penningers research groups at UBC and IMBA shed light on the role of JAGN1 in relation to B cells, which are white blood cells that can develop into plasma cells when they recognize foreign substances, such as chemicals, bacteria, viruses and pollen. In their plasma cell form, B cells can produce thousands of antibodies per second that target a specific intruder. This production occurs at a location within the cell known as the endoplasmic reticulum.

When we knocked out JAGN1 in B cells of mice, we were able to measure a drastic reduction in the number of antibodies, says the studys first author Dr. Astrid Hagelkruys, a senior research associate at IMBA.

The researchers also found that the altered sugar molecules, which coat antibodies, facilitate an antibodys ability to bind to other immune cells, thereby strengthening the bodys defensive reaction.

JAGN1 seems to influence the antibody factories in the cells, says Dr. Penninger. To our surprise, this change in the sugar structure also leads to a better ability of the antibodies to bind to other immune cells and strengthens the defense reaction.

The scientists were able to demonstrate this mechanism in human samples.

Rare genetic defects occur in only a handful of people, but they can sometimes help us decipher basic principles of biology, adds Dr. Penninger. In this case, we were able to prove that a certain gene affects the endoplasmic reticulum and is therefore essential for the mass production of antibodies.

The gene JAGN1 had been previously identified as a player in the bodys immune system by the Penninger lab in collaboration with the Klein lab at Ludwig Maximilian University in Munich among patients with severe congenital neutropenia (SCN)a disease caused by a mutation in the JAGN1 gene. Patients with SCN have abnormally low levels of white blood cells called neutrophils, and suffer from serious infections because their immune systems cannot effectively kill off bacterial or fungal invaders.

More here:
Scientists uncover essential role of one gene in antibody production - UBC Faculty of Medicine

Eli Lilly said it planned to discuss with regulators the possible emergency use of baricitinib for hospitalized patients. Other news is about early research on an antibody that might neutralize COVID and how the virus controls the brain, as well.

AP:Anti-Inflammatory Drug May Shorten COVID-19 Recovery TimeA drug company says that adding an anti-inflammatory medicine to a drug already widely used for hospitalized COVID-19 patients shortens their time to recovery by an additional day. Eli Lilly announced the results Monday from a 1,000-person study sponsored by the U.S. National Institute of Allergy and Infectious Diseases. The study tested baricitinib, a pill that Indianapolis-based Lilly already sells as Olumiant to treat rheumatoid arthritis. (Marchione, 9/14)

The Hill:Drugmaker Says Anti-Inflamatory Medicine May Shorten COVID-19 Recovery TimeThe use of Baricitinib, arheumatoidarthritis drug from Eli Lilly, led to a one-day reduction in recovery time for patients when combined with Remdesivir compared to patients who only took Remdesivir, according to a trial. The finding was statistically significant, Eli Lilly said in a statement. The company did not release the full results of the study but stated the National Institute of Allergy and Infectious Diseases (NIAID) is expected to publish full results in peer-review studies and that additional analyses are ongoing to understand clinical outcome data, including safety and morbidity data. (9/14)

In other scientific developments

Fox News:University Of Pittsburgh Scientists Discover Antibody That 'neutralizes' Virus That Causes CoronavirusScientists at the University of Pittsburgh School of Medicine have isolated the smallest biological molecule that completely and specifically neutralizes SARS-CoV-2, the virus that causes the novel coronavirus. The antibody component is 10 times smaller than a full-sized antibody, and has been used to create the drug Ab8, shared in the report published by the researchers in the journal Cell on Monday. The drug is seen as a potential preventative against SARS-CoV-2. (Deabler, 9/14)

Fox News:Coronavirus Can 'Hijack' Brain Cells To Replicate Itself, Yale Researchers DiscoverThe coronavirus can affect the brain and hijack brain cells to replicate itself, Yale University researchers have discovered. A new study from Yale University, on BioRXiv, which is awaiting peer review, found that the brain is another organ susceptible to an attack by the novel coronavirus. (McGorry, 9/14)

Stat:23andMe Research Finds Possible Link Between Blood Type And Covid-19A forthcoming study from genetic testing giant 23andMe shows that a persons genetic code could be connected to how likely they are to catch Covid-19 and how severely they could experience the disease if they catch it. Its an important confirmation of earlier work on the subject. People whose blood group is O seemed to test positive for Covid-19 less often than expected when compared to people with any other blood group, according to 23andMes data; people who tested positive and had a specific variant of another gene also seemed to be more likely to have serious respiratory symptoms. (Sheridan, 9/14)

Read the rest here:
Drug Company Touts Anti-Inflammatory Drug's Role In Shortening COVID Recovery - Kaiser Health News

LONDON The international commission convened in the aftermath of Chinese scientist He Jiankuis shock announcement of the birth of gene edited twins has set a possible course to approval of heritable gene editing, but said the technique is far from ready for use.

At this time, it is not possible to specify how to move from research to clinical application because it is not possible to make precise edits, or avoid introducing off-target effects, the committee said.

No clinical use should be considered until it is clear it can be done precisely. There are a lot of gaps at the moment, said Kay Davies, commission co-chair and professor of genetics at Oxford University, speaking at the launch of the report.

Should they ever be used, it is vitally important that these technologies are used for medically justified interventions based on rigorous understanding of how the pathogenic variant leads to disease, Davies said.

If and when heritable human genome editing is proved reliable, initial applications should be limited to the prevention of serious monogenic diseases, such as cystic fibrosis, thalassemia, sickle cell anemia and Tay-Sachs disease, but only in cases where even with in vitro fertilization and preimplantation screening of embryos, couples would have no chance of having a biologically related child that was not affected by the condition.

As the report notes, instances where both prospective parents are homozygous for a disease gene are very rare. Even for a dominant disorder that can be inherited from a single defective gene, it would be rare for one parent to be homozygous. Commission member Michele Ramsay, of the University of the Witwatersrand, South Africa, said fewer than 20 families worldwide are likely to meet the criteria.

Thats why we need international cooperation, so it is transparent and open, and data can be pooled, Ramsay said. No floodgates are going to be opened for the initial uses we recommend.

The International Commission on the Clinical Use of Human Germline Gene Editing, set up by the U.K. Royal Society and the U.S. National Academies of Science and of Medicine, involves 18 expert members from 10 countries. They spent a year reviewing the scientific literature on CRISPR and other gene editing tools, consulting peer and patients groups and meeting the public.

For the prevention of serious monogenic disease, the commission has defined a responsible clinical translation pathway, from rigorous preclinical research that determines whether and how editing can be performed efficiently and with high accuracy, to clinical application, said Richard Lifton, co-chair of the commission and president of Rockefeller University.

Key technical barriers are assessing if an edit will be corrective and demonstrating the intended edit is present in all cells. These criteria for safe and effective use have not been met yet, said commission member Haoyi Wang, of the Chinese Academy of Sciences. The report sets out the progress of research needed to show editing is effective, and [can be done] with high specificity and accurate on target charges, without causing off-target effects or mosaicism, Wang said.

No one should be attempting to follow Hes example as things stand, the commission said. All countries in which human gene editing is being researched should put in place regulation to oversee progress toward potential clinical uses, and to prevent and sanction unapproved use.

There is great concern about the potential for rogue scientists embarking on heritable gene editing on their own, Lifton said. Ultimately, regulation will be at the countrywide level, but weve got to ensure the conditions are met to ensure proper regulatory oversight. There must be a mechanism for case by case evaluation and staged rollout of the technology, he said.

More research needed

To back those national regulations, an international science advisory panel should be established to continuously follow progress, assess if preclinical requirements have been met, review data on clinical outcomes from any regulated uses of human germline editing, and advise on risks and benefits of other potential applications.

More research is needed into the technology of genome editing in human embryos, to ensure that precise changes can be made without undesired off-target effects, said Davies. International cooperation and open discussion of all aspects of genome editing will be essential.

In addition to a scientific panel to follow the science, the commission also calls for a hotline to be set up, through which researchers could raise concerns about any inappropriate use of germline editing. I would emphasize the importance of a whistleblowing mechanism, said Davies. It is suggested this could be modeled on the World Anti-Doping Agency, which polices the use of prohibited substances in sports.

The commission stresses that it was solely concerned with assessing the science and defining the specific criteria and standards required before clinical use of germline editing is considered.

A separate committee set up by the World Health Organization and co-chaired by Margaret Hamburg, former head of the U.S. FDA, is looking at ethical issues and developing governance mechanisms for both heritable and somatic gene editing. The WHO committee is expected to publish its guidance later this year.

In December 2019, He was sentenced to three years in prison and fined $430,000 for illegally carrying out the human gene editing that led to the birth of the twin girls and of another baby, with heritable changes to their genomes.

As to how far in the future approval for germline gene editing might be, Wang said the technology is moving fast. Its a bit difficult to predict, but Im quite optimistic it will become more precise. Advances also will be needed in single cell genome sequencing to ensure there are no off-target effects, he said.

Read this article:
Commission urges international cooperation, continuing research in gene editing report - BioWorld Online

MEDIA ADVISORY

FOR IMMEDIATE RELEASE: Nature Communications: Published Monday, September 14, 2020

Newswise Corresponding Author:Yasmin Hurd, PhD, Director of The Addiction Institute of Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, and other coauthors.

Bottom Line:Herion-addicted individuals have alterations in the expression a gene called FYN - a gene known to regulate the production of Tau, a protein that is highly elevated and implicated in neurocognitive disorders like Alzheimers disease. The study emphasizes that opioid use can affect the brain in a way that might increase vulnerability of neural systems that trigger neurodegeneration later in life; however, since these changes are epigenetic (alterations in gene function that are influenced by environmental factors and not alterations of the DNA itself), they are reversible and medications that have already been developed to target FYN for neurodegenerative disorders may be studied as a novel treatment for opioid addiction.

Results:Interestingly, findings were consistent across human, animal and cell models. Through post-mortem analysis of the brains of human heroin users, the team found that, specifically in neurons, the most significantly impaired epigenetic region is related to a gene called FYN. Essentially, heroin opened up the DNA at the FYN gene, which encodes a protein called tyrosine kinase FYN, that is strongly linked to synaptic plasticity and which directly results in production of Tau. Too much Tau in the brain is associated with neurodegenerative diseases. They observed that expression and activity of tyrosine kinase FYN was also induced in rats trained to self-administer heroin and also in primary striatal neurons treated with chronic morphine in vitro. Additionally, they demonstrated that inhibition of the FYN kinase (either via pharmacological means or through genetic manipulation) reduces heroin-seeking and heroin-taking behaviors.

Why the Research Is Interesting:The findings will increase awareness about the potential impact of heroin to alter neural systems related to neurodegenerative disorders. The findings also identify FYN inhibitors as a novel therapeutic treatment for heroin use disorders.

Who: Human brains from a cohort of subjects who succumbed to heroin overdose and normal controls, translational animal model of rats trained to self-administer heroin, and primary striatal neurons treated with chronic morphine in vitro.

When: Adult animals were exposed to heroin and their brains studied.

What:They performed unbiased, cell-type-specific, genome-wide profiling of chromatin accessibility, providing insights into epigenetic regulation directly in the brains of heroin-addicted individuals. To assess the causal relationship between heroin use and FYN pathology, they studied the brains of rats trained to self-administer heroin and they hit primary striatal neurons with chronic morphine in petri dishes to examine the effect at the individual cellular level.

Study Conclusions:By scanning the entire genome of heroin users to identify whether disturbances in how genes are turned on or off exist, Mount Sinai researchers found that heroin opened up the DNA at the FYN gene. The FYN gene is known to regulate the production of Tau, a protein implicated in neurodegenerative disorder like Alzheimers disease, meaning that heroin may put users at an increased risk of neurodegenerative disease later in life. Importantly, these novel findings suggest that FYN inhibitors (which have already been developed and are being assessed for use in Alzheimers disease) may be promising therapeutic tools for heroin-use disorder.

Paper Title: Chromatin accessibility mapping of the striatum identifies tyrosine kinase FYN as a therapeutic target for heroin use disorder

Said Mount Sinai's Dr. Yasmin Hurd of the research: Drug overdoses due to opioid abuse remain at epidemic levels and continue to rise precipitously during the current pandemic, with novel treatments desperately needed. Direct molecular insights into the heroin-addicted human brain are critical to guide future therapies. Our new study findings clearly open up new lines of treatment opportunities for opioid use disorder, which could benefit and potentially save the lives of so many.

###

Read the original:
People with Heroin Addiction Have Unique Molecular Alterations to The Brain That Resemble Brain Disturbances Seen in Neurodegenerative Disorders Like...

More than 1 million Americans are diagnosed with a chronic brain disorder each year, yet effective treatments for most complex brain disorders are inadequate or even nonexistent.

A major new research effort at the McGovern Institute for Brain Research at MIT aims to change how we treat brain disorders by developing innovative molecular tools that precisely target dysfunctional genetic, molecular, and circuit pathways.

The K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics in Neuroscience was established at MIT through a $28 million gift from philanthropist Lisa Yang and MIT alumnus Hock Tan 75. Yang is a former investment banker who has devoted much of her time to advocacy for individuals with disabilities and autism spectrum disorders. Tan is president and CEO of Broadcom, a global technology infrastructure company.This latest gift brings Yang and Tans total philanthropy to MIT to more than $72 million.

In the best MIT spirit, Lisa and Hock have always focused their generosity on insights that lead to real impact," says MIT President L. Rafael Reif. Scientifically, we stand at a moment when the tools and insights to make progress against major brain disorders are finally within reach. By accelerating the development of promising treatments, the new center opens the door to a hopeful new future for all those who suffer from these disorders and those who love them. I am deeply grateful to Lisa and Hock for making MIT the home of this pivotal research.

Engineering with precision

Research at the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics in Neuroscience will initially focus on three major lines of investigation: genetic engineering using CRISPR tools, delivery of genetic and molecular cargo across the blood-brain barrier, and the translation of basic research into the clinical setting. The center will serve as a hub for researchers with backgrounds ranging from biological engineering and genetics to computer science and medicine.

Developing the next generation of molecular therapeutics demands collaboration among researchers with diverse backgrounds, says Robert Desimone, McGovern Institute director and the Doris and Don Berkey Professor of Neuroscience at MIT. I am confident that the multidisciplinary expertise convened by this center will revolutionize how we improve our health and fight disease in the coming decade. Although our initial focus will be on the brain and its relationship to the body, many of the new therapies could have other health applications.

There are an estimated 19,000 to 22,000 genes in the human genome and a third of those genes are active in the brain the highest proportion of genes expressed in any part of the body. Variations in genetic code have been linked to many complex brain disorders, including depression, Parkinsons, and autism. Emerging genetic technologies, such as the CRISPR gene editing platform pioneered by McGovern Investigator Feng Zhang, hold great potential in both targeting and fixing these errant genes. But the safe and effective delivery of this genetic cargo to the brain remains a challenge.

Researchers within the new Yang-Tan Center will improve and fine-tune CRISPR gene therapies and develop innovative ways of delivering gene therapy cargo into the brain and other organs. In addition, the center will leverage newly developed single-cell analysis technologies that are revealing cellular targets for modulating brain functions with unprecedented precision, opening the door for noninvasive neuromodulation as well as the development of medicines. The center will also focus on developing novel engineering approaches to delivering small molecules and proteins from the bloodstream into the brain. Desimone will direct the center and some of the initial research initiatives will be led by associate professor of materials science and engineering Polina Anikeeva; Ed Boyden, the Y. Eva Tan Professor in Neurotechnology at MIT; Guoping Feng, the James W. (1963) and Patricia T. Poitras Professor of Brain and Cognitive Sciences at MIT; and Feng Zhang, James and Patricia Poitras Professor of Neuroscience at MIT.

Building a research hub

My goal in creating this center is to cement the Cambridge and Boston region as the global epicenter of next-generation therapeutics research. The novel ideas I have seen undertaken at MITs McGovern Institute and Broad Institute of MIT and Harvard leave no doubt in my mind that major therapeutic breakthroughs for mental illness, neurodegenerative disease, autism, and epilepsy are just around the corner, says Yang.

Center funding will also be earmarked to create the Y. Eva Tan Fellows program, named for Tan and Yangs daughter Eva, which will support fellowships for young neuroscientists and engineers eager to design revolutionary treatments for human diseases.

We want to build a strong pipeline for tomorrows scientists and neuroengineers, explains Hock Tan. We depend on the next generation of bright young minds to help improve the lives of people suffering from chronic illnesses, and I can think of no better place to provide the very best education and training than MIT.

The molecular therapeutics center is the second research center established by Yang and Tan at MIT. In 2017, they launched the Hock E. Tan and K. Lisa Yang Center for Autism Research, and, two years later, they created a sister center at Harvard Medical School, with the unique strengths of each institution converging toward a shared goal: understanding the basic biology of autism and how genetic and environmental influences converge to give rise to the condition, then translating those insights into novel treatment approaches.

All tools developed at the molecular therapeutics center will be shared globally with academic and clinical researchers with the goal of bringing one or more novel molecular tools to human clinical trials by 2025.

We are hopeful that our centers, located in the heart of the Cambridge-Boston biotech ecosystem, will spur further innovation and fuel critical new insights to our understanding of health and disease, says Yang.

The rest is here:
New molecular therapeutics center established at MIT's McGovern Institute - MIT News