COVID-19 Coronavirus molecule, March 24, 2020.

CDC | API | Gamma-Rapho via Getty Images

A team of CRISPR scientists at the New York Genome Center, New York University and Icahn School of Medicine at Mount Sinai said they have identified the genes that can protect human cells against Covid-19, a disease that has infected over 40 million and led to 1 million deaths worldwide.

The discovery comes after an eight-month screen of all 20,000 genes in the human genome led by Dr. Neville Sanjana at the New York Genome Center. Leading virologist at Mount Sinai, Dr. Benjamin tenOever, developed a series of human lung cell models for the coronavirus screening to better understand immune responses to the disease and co-authored the study.

Their study, published online last month by Cell, will appear in the scientific peer-reviewed journal's Jan. 7 print issue.

The goal was two-fold: to identify the genes that make human cells more resistant to SARS-CoV-2 virus; and test existing drugs on the market that may help stop the spread of the disease.

The breakthrough comes at a time when drug makers such as Pfizer, Oxford-AstraZeneca and Moderna are fast-forwarding vaccine and therapeutics to treat Covid-19. On Friday, Pfizer and BioNTech requested emergency authorization from the FDA for their Covid vaccine that contains genetic material called messenger RNA, which scientists expect provokes the immune system to fight the virus.

In order to better understand the complex relationships between host and virus genetic dependencies, the team used a broad range of analytical and experimental methods to validate their results. This integrative approach included genome editing, single-cell sequencing, confocal imaging and computational analyses of gene expression and proteomic datasets.

After intensive research, the scientists and doctors claim they have found 30 genes that block the virus from infecting human cells including RAB7A, a gene that seems to regulate the ACE-2 receptor that the virus binds to and uses to enter the cell. The spike protein's first contact with a human cell is through ACE-2 receptor.

"Our findings confirmed what scientists believe to be true about ACE-2 receptor's role in infection; it holds the key to unlocking the virus," said Dr. tenOever. "It also revealed the virus needs a toolbox of components to infect human cells. Everything must be in alignment for the virus to enter human cells."

The team discovered that the top-ranked genes those whose loss reduces viral infection substantially clustered into a handful of protein complexes, including vacuolar ATPases, Retromer, Commander, Arp2/3, and PI3K. Many of these protein complexes are involved in trafficking proteins to and from the cell membrane.

"We were very pleased to see multiple genes within the same family as top-ranked hits in our genome-wide screen. This gave us a high degree of confidence that these protein families were crucial to the virus lifecycle, either for getting into human cells or successful viral replication," said Dr. Zharko Daniloski, a postdoctoral fellow in the Sanjana Lab and co-first author of the study.

Using proteomic data, they found that several of the top-ranked host genes directly interact with the virus's own proteins, highlighting their central role in the viral lifecycle. The team also analyzed common host genes required for other viral pathogens, such as Zika or H1N1 pandemic influenza.

The research team also identified drugs that are currently on the market for different diseases that they claim block the entry of Covid-19 into human cells by increasing cellular cholesterol. In particular, they found three drugs currently on the market were more than 100-fold more effective in stopping viral entry in human lung cells:

The other five drugs that were tested called PIK-111, Compound 19, SAR 405, Autophinib, ALLN -- are used in research but are not yet branded and used in clinical trials for existing diseases.

Our findings confirmed what scientists believe to be true about ACE-2 receptor's role in infection; it holds the key to unlocking the virus.

Their findings offer insight into novel therapies that may be effective in treating Covid-19 and reveal the underlying molecular targets of those therapies.

The bioengineers in New York were working on other projects with gene-editing technology from CRISPR but quickly pivoted to studying the coronavirus when it swept through the metropolitan area last March. "Seeing the tragic impact of Covid-19 here in New York and across the world, we felt that we could use the high-throughput CRISPR gene editing tools that we have applied to other diseases to understand what are the key human genes required by the SARS-CoV-2 virus," said Dr. Sanjana.

Dr. Neville Sanjana and his team at the New York Genome Center used CRISPR to identify the genes that can protect human cells against Covid-19.

New York Genome Center

As he explained, "current treatments for SARS-CoV-2 infection currently go after the virus itself, but this study offers a better understanding of how host genes influence viral entry and will enable new avenues for therapeutic discovery."

Previously, Dr. Sanjana has applied genome-wide CRISPR screens to identify the genetic drivers of diverse diseases, including drug resistance in melanoma, immunotherapy failure, lung cancer metastasis, innate immunity, inborn metabolic disorders and muscular dystrophy.

"The hope is that the data from this study which pinpoints required genes for SARS-CoV-2 infection could in the future work be combined with human genome sequencing data to identify individuals that might be either more susceptible or more resistant to Covid-19," Dr. Sanjana said.

The New York team is not the first to use CRISPR gene editing techniques to fight Covid-19. Other bioengineering groups at MIT and Stanford have been using CRISPR to develop ways to fight the SARS-CoV-2 and develop diagnostic tools for Covid-19.

The potential for using CRISPR to eliminate viruses has already generated some enthusiasm in the research community. Last year, for example, Excision BioTherapeuticslicenseda technology from Temple University that uses CRISPR, combined with antiretroviral therapy, to eliminate HIV, the virus that causes AIDS.

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Gene experts claim they identified human genes that can protect against Covid-19 - CNBC

-- Sarepta is honored to be recognized for offering a range of benefits and work-life resources to employees and supporting the local community --

-- Rankings based on confidential survey information submitted by employees to independent research company --

CAMBRIDGE, Mass., Nov. 20, 2020 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, announced today that it has been named one of TheBoston Globes Top Places to Work in 2020 in the large company category.

The Boston Globes 2020 list recognizes 150 companies and organizations in Massachusetts based on surveys completed by their employees about the workplace, including 40 in the large company category. The survey measured opinions about company direction, execution, connection, management, work, pay and benefits, and engagement. Companies also provided supplemental information about responses to the global pandemic and changes implemented in how teams work.

This recognition reflects the quality of the Sarepta employees, who together have built a positive culture, navigated a challenging environment this year and, both at facilities and from home, remained focused on our daily race to save lives stolen or impacted by rare disease, said Doug Ingram, president and CEO, Sarepta. It is a testament to the resilience, tenacity and commitment of those who work at Sarepta.

Sarepta is committed to engineering precision genetic medicine to reclaim futures otherwise impacted or cut short by ushering in a new era of drug development, with the goal of shortening the time from lab to patient. The Company is building among the worlds largest gene therapy manufacturing capacity, and rethinking access and reimbursement models for revolutionary new treatments. Sareptas purpose-driven culture, where patient-focus is central to the values that shape how work is done, was resoundingly echoed by its people as a key attribute that contributed to its top ranking. Additionally, Sarepta fosters an environment that encourages its people to bring their whole selves to work and share ideas that support the entire workforce and the patient community it serves.

As the Company adjusted during the pandemic, several initiatives and new benefits were implemented as a result of employee feedback:

At Sarepta, a vision for the possibilities of pioneering science to redefine the future of medicine, and advance treatment options for patients, is shared by all. Individuals who are inspired by the opportunity to toss aside convention and break down barriers to radically change the future of medicine are encouraged to explore employment opportunities at http://www.sarepta.com.

About Sarepta TherapeuticsAt Sarepta, we are leading a revolution in precision genetic medicine and every day is an opportunity to change the lives of people living with rare disease. The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Companys programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visitwww.sarepta.comor follow us onTwitter,LinkedIn,InstagramandFacebook.

Source:Sarepta Therapeutics, Inc.

Media and Investors:Sarepta Therapeutics, Inc. Investors: Ian Estepan, 617-274-4052, iestepan@sarepta.com Media: Tracy Sorrentino, 617-301-8566, tsorrentino@sarepta.com

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Sarepta Therapeutics Named One of The Boston Globe's Top Places to Work 2020 - GlobeNewswire

As a nationwide telehealth medical practice, Genome Medical has assembled an extensive team of clinical genetic experts, including board-certified genetic counselors, medical geneticists and other specialists. This team delivers education, risk assessment, access to genetic testing and specialty care referrals -- all through virtual visits. During the COVID-19 pandemic, when two out of five Americans have avoided or delayed medical care1, access to safe virtual services is essential to ensure people at greatest risk are receiving the care they need. Genetic services support the diagnosis and care management of hereditary conditions and the identification of patients at an elevated risk for disease.

Some of the largest payers in the United States are recognizing the critical role geneticists and genetic counselors play. Their members can now self-refer and get in-network access to Genome Medical's genetic experts, and the payer's contracted providers can also make in-network referrals for their patients.

The 90 million covered lives are across multiple payers, including (in part):

"Genome Medical brings together telemedicine and genomics to tackle the rising need for genetic experts to guide patients and providers in making appropriate decisions around 1) who should get genetic testing, 2) which test is optimal and 3) how clinical care should be changed based on test results," said Steven B. Bleyl, M.D., Ph.D., chief medical officer of Genome Medical. "Patients can be seen sooner, and through telehealth, we extend the reach of genetic services to rural communities and underserved areas that have less access to in-person care. Genome Medical is a flexible and cost-effective solution for payers and their members."

Genome Medical can see 85% of cancer patients more quickly than in a traditional clinic setting.2 And in areas like pediatric genetics, where wait times of six months or more for an appointment are common, Genome Medical's growing clinical team can often see patients within a few days. The company's genetic experts are licensed in all 50 states and provide clinical genetics expertise across six major specialty areas: cancer, reproductive health, proactive health, pediatrics/rare disease, pharmacogenomics and cardiovascular genetics. Genome Medical's innovative services are trusted and utilized by health systems, hospitals, testing labs, payors, providers and employers.

Genome Medical is also committed to leveraging advanced technology-enabled solutions to transform the delivery of standard-of-care genetic health services. Beyond wider and accelerated access, the company's technology delivers a 5.5X return on investment in genetic services, while also reducing the cost of care by up to 75 percent.3,4 Its Genome Care DeliveryTM platform creates an efficient and comprehensive experience, including patient engagement and care navigation, risk assessment, self-directed education and informed consent through the Genome Care NavigatorTM, multi-modality patient support, and peer-to-peer provider consultations.

"We are pleased to see health plan partners continue to expand in-network coverage for our genetic health services," said Lisa Alderson, co-founder and CEO of Genome Medical. "It is estimated that tens of millions of patients in the United States meet medical management guidelines for referral to genetics, but most are still being missed. These patients could benefit from the advancements made in utilizing genomics for prevention, diagnosis and treatment. Giving their members access to Genome Medical and telegenetics is a significant step payers are taking in removing historical barriers."

About Genome MedicalGenome Medical is a national telegenomics technology, services and strategy company bringing genomic medicine to everyday care. Through our nationwide network of genetic specialists and efficient Genome Care DeliveryTM technology platform, we provide expert virtual genetic care for individuals and their families to improve health and well-being. We also help health care providers and their patients navigate the rapidly expanding field of genetics and utilize test results to understand the risk for disease, accelerate disease diagnosis, make informed treatment decisions and lower the cost of care. We are shepherding in a new era of genomic medicine by creating easy, efficient access to top genetic experts. Genome Medical is headquartered in South San Francisco. To learn more, visit genomemedical.com and follow @GenomeMed.

References

SOURCE Genome Medical

Genetic Counseling & Services from Anywhere | Genome Medical

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Genome Medical Reaches 90 Million Covered Lives in US - PRNewswire

SAN FRANCISCO, Nov. 19, 2020 /PRNewswire/ -- Invitae (NYSE: NVTA), a leading medical genetics company, today presented study findings that show nine percent of patients with pancreatic cancer had genetic changes in DNA damage repair (DDR) genes that would make them eligible for PARP inhibitor therapy or clinical treatment trials. Despite professional guidelines that recommend testing for all pancreatic cancer patients, it remains underutilized in routine care. The study was presented at the National Society of Genetic Counselors 39th Annual Conference.

"New therapeutics have recently become available to treat pancreatic cancer for patients with certain changes in genes such as BRCA1 and BRCA2. Yet despite the availability of these treatments and professional guidelines recommending testing, utilization is still lagging," said Robert Nussbaum, M.D., chief medical officer of Invitae and study author. "Pathogenic variants in these genes are associated with an increased risk of other cancers as well, such as breast, ovarian and prostate cancer, which means that a failure to test patients with pancreatic cancer impacts not only their treatment, but also the health of their families."

Importantly, the study of over 2,000 patients found that 15% of patients with actionable genetic changes reported no family history of cancer, which underscores the limitations of using testing criteria based on reported family history. National Comprehensive Cancer Network (NCCN) guidelines recommend genetic counseling and germline genetic testing for everyone diagnosed with pancreatic cancer as well as their first degree relatives -- approximately 3.5 million individuals in the United States.

In addition to evaluating the clinical relevance of genetic testing results, the study offered sponsored, no-charge testing to patients to evaluate the role of cost as a barrier to testing. Researchers found a small but significant increase (2%) in testing among African-American patients compared to typical rates among patients using health insurance, suggesting reducing cost may increase access to testing among this population.

The research was presented at the virtual annual meeting of the National Society of Genetic Counselors. The full research presentation from Invitae included:

Oral platform presentations:

Poster presentations:

In addition to its scientific presence, Invitae will again partner with NSGC to present the Heart of Genetic Counseling award, which honors excellence in genetic counseling and patient care as recognized by patients. Nominations include stories from patients that highlight both the clinical and personal impact a genetic counselor had on their lives and the lives of their families. This year's award will be presented during a virtual ceremony on Thursday, November 17th. The finalists include:

About Invitae

Invitae Corporation (NYSE: NVTA) is a leading medical genetics company, whose mission is to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people. Invitae's goal is to aggregate the world's genetic tests into a single service with higher quality, faster turnaround time, and lower prices. For more information, visit the company's website atinvitae.com.

Safe Harbor Statement

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the implications of the company's study results; and the importance and potential benefits of genetic testing for pancreatic cancer patients. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially, and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: the company's history of losses; the company's ability to compete; the company's failure to manage growth effectively; the company's need to scale its infrastructure in advance of demand for its tests and to increase demand for its tests; the company's ability to use rapidly changing genetic data to interpret test results accurately and consistently; security breaches, loss of data and other disruptions; laws and regulations applicable to the company's business; and the other risks set forth in the company's filings with the Securities and Exchange Commission, including the risks set forth in the company's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020. These forward-looking statements speak only as of the date hereof, and Invitae Corporation disclaims any obligation to update these forward-looking statements.

Contact:

Laura D'Angelo[emailprotected](628) 213-3283

SOURCE Invitae Corporation

http://www.invitae.com

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New Study Highlights the Importance of Genetic Testing for Pancreatic Cancer Patients - PRNewswire

HOUSTON, Nov. 17, 2020 /PRNewswire/ --With the arrival of flu season, Baylor Genetics, a pioneer of genetic testing and precision medicine, has launched the latest combination test for the novel coronavirus, SARS-CoV-2, and Influenza A and B.

"Baylor Genetics created the combination COVID-19 and flu test because the symptoms between the two are so similar, but the treatments are undeniably different," stated Kengo Takishima, President & Chief Executive Officer at Baylor Genetics. "This groundbreaking test, with results available in 48 hours or less, will result in better data and more accurate treatments for these similar, but distinct, viruses."

In response to the global pandemic, Baylor Genetics validated its first test for COVID-19 in June 2020. Once launched, the company continued to focus on innovative efforts to help prevent the spread of the disease. Some of these efforts include unique partnerships with the City of Houston and Rice University. With their latest COVID-19 (SARS-CoV-2) & Flu (Influenza A/B) RT-PCR test, individuals will be able todetermine if they are currently infected with COVID-19 or the flu.

"The clinical presentations of COVID-19 and influenza are similar, and it is difficult to differentiate the two entities on symptoms alone," stated Dr. Christine Eng, Chief Medical Officer and Chief Quality Officer at Baylor Genetics. "This combination test will identify if SARS-CoV-2 or influenza A/B is the culprit, thus helping you and your healthcare provider better direct your care. Of course, it's important to stay proactive this season and get your flu shot if you haven't already."

Since many are traveling during the holidays, it is imperative that individuals know whether they are infected with either COVID-19 or the flu and how to treat each virus. While these respiratory viruses have similar symptoms, their treatments are different. For COVID-19, potential treatment and vaccine options are emerging. For the flu, antiviral medications can help address symptoms and potentially shorten the time an individual is sick. Therefore, it is crucial for individuals to be able to confirm which virus they may be infected with to take the proper next steps to restore their health.

For the COVID-19 and flu combination test, all sample results will be sent to individuals securely and electronically within 48 hours of Baylor Genetics' receiving the sample. In addition, the results will be automatically reported to state officials to track and slow the spread of cases in the local community. With accepted sample types of nasal or nasopharyngeal swab, all of the supplies for testing and returning the kit is provided to the individual.

To learn more about Baylor Genetics' test for COVID-19, visit https://www.baylorgenetics.com/covid19/.

About Baylor GeneticsBaylor Genetics is a joint venture of H.U. Group Holdings, Inc. and Baylor College of Medicine, including the #1 NIH-funded Department of Molecular and Human Genetics. Located in Houston's Texas Medical Center, Baylor Genetics serves clients in 50 states and 16 countries.

To learn more about Baylor Genetics visit http://www.baylorgenetics.com.

SOURCE Baylor Genetics

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Baylor Genetics Launches Combination Test for COVID-19 and Influenza A and B; Multi-Panel Test Seeks to Address Dilemma of "Overlapping symptoms...

Precise treatment leads to resolution of patient's debilitating symptoms and complete remodeling of her lymphatic system

PHILADELPHIA, Nov. 20, 2020 /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP) have resolved a severe lymphatic disorder in a girl with Noonan Syndrome that had led to upper gastrointestinal bleeding, fluid collection around the lungs, and numerous surgeries that had been unable to resolve her symptoms. By identifying a genetic mutation along a pathway related to lymphatic vessel development and function, the research team was able to target the pathway using an existing drug they had used in a previous case to remodel a patient's lymphatic system.

The case study, which was published today in Pediatrics, describes a resolution of the patient's symptoms within three months while on the medication.

"This study is quite significant," said first author Yoav Dori, MD, PhD, Director of the Jill and Mark Fishman Center for Lymphatic Disorders at CHOP. "Inhibiting this pathway seems to have sweeping, widespread effects on the lymphatic system. How this process occurs is not fully understood, but is remarkable in its speed and breadth. This gives us a lot of hope for treating other patients with genetic mutations along this same pathway in the future."

The patient described in the paper, Maria, first came to CHOP when she was 14, after experiencing severe anemia due to upper gastrointestinal bleeding, as well as other symptoms including fluid build-up in the cavity around her lungs, chronic fatigue, delayed puberty, and difficulty gaining weight. Maria had been born with Noonan Syndrome, a genetic disorder that prevents normal development in various parts of the body and often results in short stature, heart defects and other physical problems, including an abnormal lymphatic system. Despite aggressive medical therapy elsewhere, Maria continued to bleed internally, and she underwent multiple blood transfusions to try to stabilize her health.

Within two days of transferring to CHOP, the lymphatics team, led by Dori, determined Maria had many lymphatic irregularities, which were leading to internal bleeding and lung problems, so they scheduled Maria's first intervention, a lymphatic embolization procedure that would seal the leaky vessels in her gut.

However, within two months of the procedure, Maria's gastrointestinal bleeding recurred. Over the following 8 months, she underwent two additional procedures, as well as a cauterization procedure to close off some of the blood vessels in her gut, but the benefits of each procedure lasted only about three months before the bleeding and her symptoms returned.

Based on whole exome sequencing done at CHOP's Center for Applied Genomics, the research team learned that Maria had a genetic mutation in the SOS1 gene, which operates along the RAS-MAPK pathway. This pathway involves mitogen-activated protein kinase (MEK), and Maria's mutation caused an overproduction of MEK, which resulted in the uncontrolled proliferation of her lymphatic vessels.

The research team had previously used a MEK inhibitor in another patient with a severe lymphatic disorder with great success. That patient had a mutation in the ARAF gene, which is also on the RAS-MAPK pathway. Within months of beginning treatment with trametinib, a MEK inhibitor, the patient saw a resolution of his symptoms and a complete remodeling of his lymphatic system.

Given that SOS1 operates on the same pathway as ARAF, Jean Belasco, MD, an oncologist in CHOP's Cancer Center who co-led the study, applied for compassionate use of the drug in Maria's case, given the lack of other treatment options.

"The success of trametinib in another patient with a mutation on the RAS-MAPK pathway encouraged us to try this approach, since other procedures and therapies continued to be unsuccessful," Belasco said. "Although we are in the early days of this type of personalized medicine, the hope is that by looking at patients' mutations, we can find more drugs and better care for patients with genetic diseases."

Within three months of starting the drug, Maria's vital signs stabilized. The bleeding stopped, her electrolyte, hemoglobin, and albumin levels returned to normal, and she began to gain weight. Maria's mother noticed that Maria wasn't going through periods of exhaustion anymore, and her pallor improved.

"She looks better than she's ever looked," her mother said. "She looks like a normal teenager. It's like night and day. She's also a lot happier. I think she knew deep down she was dying. The medicine gave her hope."

Hakon Hakonarson, Director of the Center for Applied Genomics and co-author of the paper, said that although Maria's SOS1 mutation is distinctly different than the ARAF mutation seen in the other patient, the drug was equally effective because it targets and blocks the function of MEK. He likened the scenario to a pathway where 15 events need to occur for a cell to function. Maria's SOS1 mutation might occur at step nine, whereas the ARAF mutation might occur at step three, but both genes are on a chain that ultimately passes through a tunnel that leads to phosphorylation and overactivity of MEK. Since both mutations were so-called gain of function mutations, MEK and thus lymphatic activity was overexpressed in both patients. The MEK inhibitor put the brakes on a system in overdrive.

"Remarkable advances in genetics have allowed us to uncover these mutations and cluster them into selective pathways and determine effective therapies based on genetic mutations with very high precision," said Hakonarson. "No one could have guessed that this drug would have worked for Maria without knowing the underlying genetics. This discovery is extremely important because Noonan Syndrome has the biggest patient population with alterations in MEK signaling. Not all Noonan patients will have mutations that respond to this therapy, but a very good number of them will."

He added that the treatment could also benefit patients with other genetic defects, though he noted the ongoing use of the drug treats the symptoms caused by these mutations, but does not fix the gene or cure the underlying condition.

"MEK inhibition has the potential to have significant effects on other organ systems affected by RAS-MAPK gene defects, such as the heart, eyes, skin and the coagulation system," Hakonarson said.

Hakonarson is also part of CHOP's Comprehensive Vascular Anomalies Program (CVAP), a CHOP Frontier Program that uses state-of-the-art genomics and personalized research strategies to determine the causes of complex vascular conditions and identify targeted therapies. The program works closely with the Lymphatic Imaging and Interventions Frontier Program, which is led by Dori. CHOP's Frontier Programs conduct cutting-edge research that translates into advanced clinical care. The CVAP, in particular, draws on the extensive clinical and genomic research capacity within the Cancer Center and Center for Applied Genomics.

Even with the success of the breakthrough treatment pioneered by these programs, it is not entirely clear why MEK inhibitors not only resolve patients' symptoms but also completely remodel their lymphatic systems. Hakonarson said one possibility is that when mutated genes cause uncontrolled growth of the lymphatic system, the body's vessels leak fluid everywhere in the body. When you shut down the unregulated growth, other homeostatic mechanisms that are balancing the system come into effect, so the overreactive cells that were growing out of control die and are replaced by normal cells that gradually build up the lymphatic system.

Whatever the mechanism, Maria's mother said her daughter had no hesitation at being the first patient with Noonan Syndrome to try this treatment to resolve a lymphatic issue.

"Maria saw the value from the beginning," she said. "She saw the value for herself, but she was also thinking of other Noonan kids, some of whom have passed away from lymphatic issues. She was willing and eager."

Dori et al. "Severe Lymphatic Disorder Resolved with MEK Inhibition in a Noonan Patient with SOS1 Mutation," Pediatrics, published online November 20, 2020, doi: 10.1542/2020-000123

About Children's Hospital of Philadelphia: Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. In addition, its unique family-centered care and public service programs have brought the 564-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu

Contact: Natalie SolimeoChildren's Hospital of Philadelphia267-426-6246solimeon@chop.edu

View original content:http://www.prnewswire.com/news-releases/chop-researchers-reverse-severe-lymphatic-disorder-in-patient-with-noonan-syndrome-by-targeting-genetic-pathway-301177697.html

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CHOP Researchers Reverse Severe Lymphatic Disorder in Patient with Noonan Syndrome by Targeting Genetic Pathway - BioSpace

This article was originally published here

Eur Respir J. 2020 Nov 19:2003406. doi: 10.1183/13993003.03406-2020. Online ahead of print.

ABSTRACT

Epigenetic mechanisms represent potential molecular routes which could bridge the gap between genetic background and environmental risk factors contributing to the pathogenesis of pulmonary diseases. In patients with chronic obstructive pulmonary disease (COPD), asthma, and pulmonary arterial hypertension (PAH), there is emerging evidence of aberrant epigenetic marks, mainly including DNA methylation and histone modifications which directly mediate reversible modifications to the DNA without affecting the genomic sequence. Post-translational events and microRNAs can be also epigenetically regulated and potentially participate to disease pathogenesis. Thus, novel pathogenic mechanisms and putative biomarkers may be detectable in peripheral blood, sputum, nasal and buccal swabs, or lung tissue. Besides, DNA methylation plays an important role during the early phases of fetal development and may be impacted by environmental exposures, ultimately influencing an individuals susceptibility to COPD, asthma, and PAH later in life. With the advances in omics platforms and the application of computational biology tools, modelling the epigenetic variability in a network framework, rather than as single molecular defects, is providing insights into the possible molecular pathways underlying the pathogenesis of COPD, asthma, and PAH. Epigenetic modifications may have clinical applications as non-invasive biomarkers of pulmonary diseases. Moreover, combining molecular assays with network analysis of epigenomic data may aid in clarifying the multi-stage transition from a pre-disease to disease state, with the goal of improving primary prevention of lung diseases and its subsequent clinical management.We describe epigenetic mechanisms known to be associated with pulmonary diseases and discuss how network analysis could improve our understanding of lung diseases.

PMID:33214212 | DOI:10.1183/13993003.03406-2020

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Epigenetics and pulmonary diseases in the horizon of precision medicine: a review - DocWire News

SALT LAKE CITY, Nov. 16, 2020 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (NASDAQ: MYGN), a global leader in molecular diagnostics and precision medicine, announced today the expansion of Myriad myChoice tumor testing in several European markets and China.

Myriad myChoice CDx is the industrys most clinically-validated genomic instability test. The test enables physicians to identify patients with tumors that have lost the ability to repair double-stranded DNA breaks, resulting in potentially increased susceptibility to DNA-damaging drugs such as platinum drugs or PARP inhibitors, including Lynparza (olaparib). A biomarker subgroup analysis of the PAOLA-1 Phase III trial (Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer, 2019) of Lynparza included patients with advanced ovarian cancer and homologous recombination deficient (HRD)-positive tumors as detected by the myChoice test, including those with BRCA gene mutations. The trial showed that Lynparza in combination with bevacizumab maintenance treatment improved progression-free survival to a median of 37.2 months versus 17.7 months for bevacizumab alone in patients with HRD-positive advanced ovarian cancer. Recently, the European Commission authorized use of Lynparza for the first-line maintenance treatment with bevacizumab of patients with HRD-positive advanced ovarian cancer. Lynparza is jointly developed and commercialized by AstraZeneca (LSE/STO/Nasdaq: AZN) and Merck.

As part of the expansion in Europe, Myriad will license and provide technological support to leading pathology institutes in Germany and France. Additionally, Myriad will support European customers by performing testing out of its clinical laboratory at the companys global headquarters in Salt Lake City. Also, the institutes in Europe will perform the tests with Myriads myChoice CDx PLUS assay. Myriad myChoice CDx PLUS is CE-marked in accordance with the In-Vitro Diagnostic Devices Directive (98/79/EC).

Another collaboration in China provides that Myriad will partner with Burning Rock Biotech, a leader in next generation sequencing technology for precision oncology, to provide myChoice for HRD testing in Phase III clinical studies and clinics throughout China. Myriad will provide Burning Rock with access to its proprietary myChoice technology. The partnership with Burning Rock expands global access to myChoice and positions the test as a preferred developmental companion diagnostic in this important drug development category.

These new strategic partnerships with leading companies dedicated to advancing the power of precision medicine, reinforce Myriads commitment to expanding access to genetic insights for more patients than ever before, said Nicole Lambert, president of Myriad Genetic Laboratories. Through close collaboration with innovative laboratories in Europe and with Burning Rock in China, we are bringing the clinical benefits of myChoice testing to additional markets and patients, advancing personalized treatment for patients around the world.

In August 2020, myChoice was exclusively cited and the only named commercial companion diagnostic by the American Society of Clinical Oncology in new recommendations on the use of PARP inhibitors for the treatment and management of certain patients with advanced ovarian cancer. The new recommendations, based on clinical trial results, were published in the Journal of Clinical Oncology.

AboutMyriad myChoice Myriad myChoice is the most comprehensive homologous recombination deficiency (HRD) test, enabling physicians to identify patients with tumors that have lost the ability to repair double-stranded DNA breaks, resulting in increased susceptibility to DNA-damaging drugs such as platinum drugs or PARP inhibitors. The myChoice test comprises tumor sequencing of the BRCA1 and BRCA2 genes and a composite of three proprietary technologies (loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions). For more information, visit: https://myriad-oncology.com/mychoice-cdx/

About Myriad Genetics Myriad Genetics Inc., is a leading personalized medicine company dedicated to being a trusted advisor transforming patient lives worldwide with pioneering molecular diagnostics. Myriad discovers and commercializes molecular diagnostic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across six major medical specialties where molecular diagnostics can significantly improve patient care and lower healthcare costs. Myriad is focused on three strategic imperatives: transitioning and expanding its hereditary cancer testing markets, diversifying its product portfolio through the introduction of new products and increasing the revenue contribution from international markets. For more information on how Myriad is making a difference, please visit the Company's website:www.myriad.com.

Myriad, the Myriad logo, BART, BRACAnalysis, Colaris, Colaris AP, myPath, myRisk, Myriad myRisk, myRisk Hereditary Cancer, myChoice, myPlan, BRACAnalysis CDx, Tumor BRACAnalysis CDx, myChoice CDx, Vectra, Prequel, Foresight, GeneSight, riskScore and Prolaris are trademarks or registered trademarks of Myriad Genetics, Inc. or its wholly owned subsidiaries in the United States and foreign countries. MYGN-F, MYGN-G.

Safe Harbor Statement This press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to the Companys new international collaborations on the myChoice CDx test, including offering the test to European patients, and partnering with pathology institutes in Europe and Burning Rock in China; and the Companys strategic directives under the caption "About Myriad Genetics." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by forward-looking statements. These risks and uncertainties include, but are not limited to: uncertainties associated with COVID-19, including its possible effects on our operations and the demand for our products and services; our ability to efficiently and flexibly manage our business amid uncertainties related to COVID-19; the risk that sales and profit margins of our molecular diagnostic tests and pharmaceutical and clinical services may decline; risks related to our ability to transition from our existing product portfolio to our new tests, including unexpected costs and delays; risks related to decisions or changes in governmental or private insurers reimbursement levels for our tests or our ability to obtain reimbursement for our new tests at comparable levels to our existing tests; risks related to increased competition and the development of new competing tests and services; the risk that we may be unable to develop or achieve commercial success for additional molecular diagnostic tests and pharmaceutical and clinical services in a timely manner, or at all; the risk that we may not successfully develop new markets for our molecular diagnostic tests and pharmaceutical and clinical services, including our ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying our molecular diagnostic tests and pharmaceutical and clinical services and any future tests and services are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with operating our laboratory testing facilities and our healthcare clinic; risks related to public concern over genetic testing in general or our tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of the healthcare system or healthcare payment systems; risks related to our ability to obtain new corporate collaborations or licenses and acquire new technologies or businesses on satisfactory terms, if at all; risks related to our ability to successfully integrate and derive benefits from any technologies or businesses that we license or acquire; risks related to our projections about our business, results of operations and financial condition; risks related to the potential market opportunity for our products and services; the risk that we or our licensors may be unable to protect or that third parties will infringe the proprietary technologies underlying our tests; the risk of patent-infringement claims or challenges to the validity of our patents or other intellectual property; risks related to changes in intellectual property laws covering our molecular diagnostic tests and pharmaceutical and clinical services and patents or enforcement in the United States and foreign countries, such as the Supreme Court decisions in Mayo Collab. Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012), Assn for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013), and Alice Corp. v. CLS Bank Intl, 573 U.S. 208 (2014); risks of new, changing and competitive technologies and regulations in the United States and internationally; the risk that we may be unable to comply with financial operating covenants under our credit or lending agreements; the risk that we will be unable to pay, when due, amounts due under our credit or lending agreements; and other factors discussed under the heading "Risk Factors" contained in Item 1A of our most recent Annual Report on Form 10-K for the fiscal year ended June 30, 2020, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

Media Contact: Jared Maxwell (801) 505-5027 jmaxwell@myriad.comInvestor Contact: Scott Gleason(801) 584-1143sgleason@myriad.com

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Myriad Genetics Announces Global Expansion of Myriad myChoice Tumor Testing in Europe and China - GlobeNewswire

Mohamed Elrashed Shogar, graduating in genetics, stands inside a Molecular Biology Building laboratory where he has conducted much of his undergraduate research. Photo by Christopher Gannon. Larger image. All photos and videos were shot following physical distancing guidelines, and with staff wearing face coverings.

AMES, Iowa A headache started Mohamed Shogars journey to a career in medicine.

His mothers relentless headaches forced her to travel more than 900 miles from their home to Sudans capital, Khartoum, for treatment. She never found relief, and it frustrated Shogar, who is graduating from Iowa State University next weekend with a bachelors degree in genetics.

Shes the reason, Shogar said. She motivated me to pursue a career in medicine.

He was also bothered by the physician shortage in his hometown of Al Fashir. Shogar noticed the same physician shortage when he arrived in the United States and again thought, Why not pursue a career in medicine to help them out?

Shogars mother has a Ph.D. and his father is a high school principal. Education was the biggest priority for his family. So, after graduating high school, Shogar came to the U.S. in 2016.

After traveling to Egypt to meet with the U.S. ambassador and receive a green card, Shogar was on his way.

The first time, when I landed in Chicago, I was so overwhelmed, he said. I didnt know what to expect. I didnt know the language or the culture. I had just finished high school, and the future wasnt clear to me.

He headed to Cedar Rapids, where he lived with his cousin for a few months and talked to newfound friends about his educational options in the state. One friend suggested starting out at a community college before heading to a four-year university. So, Shogar enrolled at Kirkwood Community College and took English as a Second Language classes while working full time at the Nordstrom warehouse. He gained medical experience as a phlebotomist at Mercy Medical Center in Cedar Rapids before taking some courses at the University of Iowa.

In 2018, he transferred to Iowa State to finish his genetics degree. At the same time, hes worked as a phlebotomist at Mary Greeley Medical Center.

I wouldnt have done it without the people who helped me out, he said. Im so grateful for them.

During his first semester in Ames, Shogar had to take organic chemistry considered one of the most difficult courses at Iowa State. He struggled during the first exam and felt defeated. But he went to the office of chemistry professor Arthur Winter for help. They talked about college courses generally, and how to study. On Shogars next organic chemistry exam, he received a near-perfect score.

Shogar found community and friendship in his classes as well as student organizations, such as the Sudan United Association and the Minority Association for Pre-Health Students.

He typically travels back to Sudan every winter to visit his family, but with the ongoing COVID-19 pandemic and his post-graduation plans, that visit is on hold. Right now, hes in the midst of the nerve-wracking process of applying to medical schools.

Shogar said going to school and working through the pandemic has been mentally and emotionally draining.

It also had an impact on my education journey, he said. I was not able to shadow and volunteer, which is a very important part in medical school applications.

He also found a mentor in Mark Hargrove, Morrill Professor of biochemistry, biophysics and molecular biology (BBMB), who talked with Shogar about his plans after graduation. To build his research experience, Gordon connected Shogar with Alan DiSpirito, professor of BBMB, whose lab works with methanobactin to study its effects on Wilsons disease, a genetic disorder that causes excessive copper build-up in the body.

This has been an amazing experience, honestly, Shogar said. Its been such a welcoming environment.

The opportunities that I got here, I dont think I would be able to get in Sudan. In terms of the quality of education, I cant even compare it.

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Four years after landing in US, graduating ISU senior is on his way to medical school - Iowa State University News Service

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Discovery of receptor, generation of decoy could help contain outbreaks of Venezuelan equine encephalitis virus

Researchers at Washington University School of Medicine in St. Louis have identified a molecule that protects mice from brain infections caused by Venezuelan equine encephalitis virus (VEEV), a mosquito-borne virus notorious for causing fast-spreading, deadly outbreaks in Mexico, Central America and northern South America.

Researchers at Washington University School of Medicine in St. Louis have identified a molecule that protects mice from brain infections caused by Venezuelan equine encephalitis virus (VEEV), a mosquito-borne virus notorious for causing fast-spreading, deadly outbreaks in Mexico, Central America and northern South America. As the climate changes, the virus is likely to expand its range and threaten more countries in the Americas, including the U.S.

Public health officials have struggled to contain such outbreaks in the absence of effective drugs and vaccines. As a potential drug, the molecule described in a paper published Nov. 18 in the journal Nature could serve as a much needed tool to control the deadly virus.

This virus can infect many species of wild mammals, and every few years it jumps from animals to humans via mosquitoes and causes thousands of infections and many deaths, said senior author Michael S. Diamond, MD, PhD, the Herbert S. Gasser Professor of Medicine and a professor of molecular microbiology, and of pathology and immunology. Theres concern that with global warming and population growth, well get more outbreaks.

Once injected under the skin by mosquitoes, the virus homes in on neurons. People start experiencing symptoms such as headache, muscle pain, fatigue, vomiting, nausea, diarrhea, sore throat and fever within a week. In the most serious cases, the virus gets past the blood-brain barrier, causing encephalitis brain inflammation that can be fatal in up to a quarter of patients.

To find the potential drug, Diamond and colleagues including first authors Hongming Ma, PhD, an instructor in medicine, and Arthur S. Kim, PhD, a postdoctoral researcher began by searching for the protein handle on the surface of animal cells that the virus attaches to and uses to get inside cells. A drug that stops the virus from grabbing that handle, the scientists reasoned, could stymie infection and prevent disease.

But first they had to make a form of the virus they could work easily with. During the Cold War, the U.S. and the Soviet Union attempted to weaponize the virus, and it is still classified as a select agent, meaning only certain high-security labs are allowed to work with it. So instead, the researchers and their colleagues took Sindbis virus, a related virus that causes mild fever and rash, and swapped out some of its genes for some from VEEV. The resulting hybrid virus, called Sindbis-VEEV, infects cells like authentic VEEV but is unable to cause severe disease.

Using a genetic engineering technique known as genome-wide CRISPR screening, the researchers deleted genes in mouse neuronal cells until they found one called Ldlrad3 whose absence kept Sindbis-VEEV from infecting cells. The missing gene codes for a little-studied surface protein.

Further experiments verified the importance of Ldlrad3. Adding the gene back to neuronal cells restored the viruss ability to infect cells. The human LDLRAD3 gene is almost identical to its mouse equivalent, and knocking out the human gene also reduced infection in multiple cell lines. When the researchers added Ldlrad3 to a different cell type that is normally resistant to infection, the virus was able to infect the cell. Co-author William Klimstra, PhD, at the University of Pittsburgh, separately replicated the findings using authentic, highly virulent VEEV.

Ldlrad3 doesnt appear to be the only way the virus gets inside cells, since a small amount of virus is able to infect cells lacking the protein. But it is clearly the primary way in. Since Ldlrad3 is naturally on our cells and cant be removed, the scientists decided to create a decoy handle using a piece of the Ldlrad3 protein. Any virus particles that mistakenly latch onto the decoy handle would fail to infect cells and instead would get destroyed by the immune system.

To test their decoy in a living animal, the researchers injected mice with authentic virulent VEEV in two different ways: under the skin to mimic a mosquito bite, or directly into the brain. They gave the mice the decoy handle or a placebo molecule for comparison, either six hours before or 24 hours after infection. In all experiments, all of the mice that received the placebo died within a week. In most cases, all of the mice that received the decoy molecule survived, although in the most stringent experiment in which the virus was injected into the brain two of the 10 mice died despite receiving the decoy.

In an outbreak situation, you may be able to use a drug like this as a countermeasure to prevent transmission and further spread, Diamond said.

A major advantage to an antiviral drug based on a human rather than a viral protein is that it is unlikely the virus could evolve resistance to it. Any mutation that enables the virus to avoid the decoy probably would make it unable to attach to cells, too, the researchers said.

Ma H, Kim AS, Kafai NM, Earnest JT, Shah A, Case JB, Basore K, Gilliland TC, Sun C, Nelson CA, Thackray LB, Klimstra WB, Fremont DH, Diamond MS. LDLRAD3 is a receptor for Venezuelan equine encephalitis virus. Nature. Nov. 18, 2020. DOI: 10.1038/s41586-020-2915-3

This study was supported by the National Institutes of Health (NIH), grant numbers R01AI143673, U19AI142790, R01AI095436 and T32 AI007172 and contract number HHSN272201700060C; and the Defense Reduction Threat Agency, grant numbers HDTRA1-15-1-0013 and HDTRA1-15-1-0047.

Washington University School of Medicines 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Childrens hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Childrens hospitals, the School of Medicine is linked to BJC HealthCare.

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Lethal brain infections in mice thwarted by decoy molecule - Washington University School of Medicine in St. Louis