Scientists sharpen their molecular scissors and expand the gene editing toolbox

Phys.org | February 22, 2019

Wake Forest Institute for Regenerative Medicine (WFIRM) scientists have figured out a better way to deliver a DNA editing tool to shorten the presence of the editor proteins in the cells in what they describe as a "hit and run" approach. CRISPR (clustered regularly interspaced short palindromic repeats) technology is used to alter DNA sequences and modify gene function. CRISPR/Cas9 is an enzyme that is used as a pair of scissors to cut two strands of DNA at a specific location to add, remove or repair bits of DNA. But CRISPR/Cas9 is not 100 percent accurate and could potentially cut unexpected locations, causing unwanted results.
"One of the major challenges of CRISPR/Cas9 mRNA technologies is the possibility of off-targets which may cause tumors or mutations," said Baisong Lu, Ph.D., assistant professor of regenerative medicine at WFIRM and one of the lead authors of the paper. Although other types of lentivirus-like bionanoparticles (LVLPs) have been described for delivering proteins or mRNAs, Lu said, "the LVLP we developed has unique features which will make it a useful tool in the expanding genome editing toolbox."

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RESEARCH

Cedilla Therapeutics Expands Leadership Team with Key Appointments Across R&D And Finance

Cedilla Therapeutics | November 17, 2021

Cedilla Therapeutics, a biotechnology company bringing a new dimension to precision oncology, announced appointments across its research and development (R&D) and finance teams, including Joshua Murtie, Ph.D., as Vice President of Biology and Chris Lindblom as Vice President of Finance. These hires are part of an ongoing initiative to expand Cedilla’s leadership and enable future growth as the company progresses its lead programs, conditional inhibitors of TEAD and CDK2, toward the clinic and continues to develop a broad portfolio of small molecule medicines that target key oncogenic drivers. “We are delighted to expand our team with these key hires, who share our passion and commitment to developing targeted medicines that conditionally modulate proteins in their functional state. We look forward to Joshua and Chris’ many contributions as we continue to explore the power of our novel approach to access historically undruggable cancer drivers, advance our lead conditional inhibitor programs targeting TEAD and CDK2 into clinical development, and ultimately build Cedilla into a fully integrated organization and leader in precision medicine.” Alexandra Glucksmann, Ph.D., President and Chief Executive Officer of Cedilla Therapeutics Joshua Murtie, Ph.D., has been appointed Vice President of Biology. Dr. Murtie brings over ten years of industry experience to Cedilla. He worked most recently as Senior Director at Servier Pharmaceuticals, where he oversaw cancer biology, in vivo pharmacology and early-stage program management at the company’s U.S. research site. Earlier, he spent nearly seven years at Agios Pharmaceuticals in roles of increasing responsibility, ultimately serving as Senior Director and Head of Cancer Biology, with responsibility for the strategic oversight of the company’s cancer biology portfolio from early target discovery to translational research. Prior to Agios Pharmaceuticals, Dr. Murtie worked as an investigator at Sanofi and Novartis. He holds a Ph.D. in molecular and cell biology from the Uniformed Services University of the Health Sciences and completed his research fellowship at Harvard Medical School. “I am thrilled to join Cedilla, particularly as we prepare to advance our lead programs, targeting TEAD and CDK2, into investigational new drug application-enabling studies next year,” said Dr. Murtie. “Both TEAD and CDK2 are well-known yet elusive cancer targets, which, if drugged successfully, could benefit the lives of patients living with a broad range of solid tumors. I am incredibly impressed by the collaborative and innovative culture at Cedilla and look forward to working closely with the team to translate our research efforts into precision therapies for patients in need.” Chris Lindblom has been appointed Vice President of Finance. Over the course of his 19 years in the biotechnology industry, Mr. Lindblom has crafted long-range financial plans for public and private companies and played a key role in helping companies raise capital through private equity rounds, venture debt deals and public offerings. Prior to joining Cedilla, Mr. Lindblom served as Vice President of Finance at IFM Therapeutics, Cogen Immune Medicine (through its merger with Torque Therapeutics to form Repertoire Immune Medicines) and Warp Drive Bio (through its acquisition by Revolution Medicines). Earlier, Mr. Lindblom held various senior finance roles at Millennium Pharmaceuticals, including through the commercial launch of VELCADE®, and at Infinity Pharmaceuticals. He also served as Vice President of Finance at OvaScience and Senior Vice President of Finance and Administration at BIND Therapeutics. Mr. Lindblom holds an MBA from Boston College and a B.S. in accounting from Syracuse University. He is also a CPA. “Since its founding, Cedilla has attracted a strong team, including leading scientists and advisors and a robust investor syndicate, to support its mission to bring a new dimension to precision oncology and deliver medicines that can offer profound benefits to patients,” said Mr. Lindblom. “I am honored to take on this role and eager to partner with my new colleagues as we continue building Cedilla for its next phase of growth.” About Cedilla Therapeutics Cedilla Therapeutics is bringing a new dimension to precision oncology. We have discovered new ways to selectively inhibit oncogenic drivers with small molecules that conditionally modulate proteins in their functional state. Our conditional inhibitors are unlocking critical and elusive cancer targets including TEAD and CDK2. We are a driven and patient-focused team.

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MEDICAL

PhageNova Bio, Inc. Announces Publication Describing New Method for Safe and Effective Pulmonary Delivery of Therapeutics

PhageNova Bio, Inc. | December 14, 2020

PhageNova Bio, Inc. ("PhageNova") is pleased to declare the distribution of information created through a sponsored research agreement with Rutgers, The State University of New Jersey. The Med (a Cell Press distribution) article, entitled Targeted Phage Display-Based Pulmonary Vaccination in Mice and Non-human Primates, portrays another technique for protected and effective pulmonary delivery of therapeutics, including an aerosol vaccination strategy which is being developed to address the current SARS-CoV-2 pandemic. "Our targeted method of pulmonary delivery is the initial step towards the development of aerosol phage-based vaccines for human applications against multiple diseases," says Renata Pasqualini, PhD, co-senior study author, Founder and Chief Scientific Officer of PhageNova, and Chief of the Division of Cancer Biology, Department of Radiation Oncology at Rutgers Cancer Institute and Rutgers New Jersey Medical School. "Other advantages of phage particles are that they are highly stable under harsh environmental conditions, and their large-scale production is extremely cost-effective compared with other vaccine strategies because they don't need to be refrigerated, which is a particularly important requirement for the developing world."

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CELL AND GENE THERAPY

Childhood Trauma and Genetics Linked to Increased Obesity Risk

DRI | March 10, 2022

New research from the Healthy Nevada Project® found associations between genetics, obesity, and childhood trauma, linking social health determinants, genetics, and disease. The study, which was published this week in Frontiers in Genetics, found that participants with specific genetic traits and who experience childhood traumas are more likely to suffer from adult obesity. In 2016, DRI and Renown Health launched the Healthy Nevada Project®, the nation’s first community-based, population health study, which now has more than 60,000 participants. The project is a collaboration with personal genomics company, Helix, and combines genetic, environmental, social, and clinical data to address individual and community health needs with the goal of improving health across the state and the nation. The new study focuses on Adverse Childhood Experiences (ACEs), which are traumatic and unsafe events that children endure by the age of 18. Over 16,000 participants in the Healthy Nevada Project® answered a mental health survey, and more than 65 percent of these individuals self-reported at least one ACE occurrence. These 16,000 participants were cross-referenced with their genetic makeup, and clinical Body Mass Index (BMI) measures. According to the research team’s findings, study participants who had experienced one or more types of ACE were 1.5 times more likely to become obese adults. Participants who experienced four or more ACEs were more than twice as likely to become severely obese. Our analysis showed a steady increase in BMI for each ACE a person experienced, which indicates a very strong and significant association between the number of adverse childhood experiences and adult obesity, More importantly, participants’ BMI reacted even more strongly to the occurrence of ACEs when paired with certain mutations in several genes, one of which is strongly associated with schizophrenia.” lead author Karen Schlauch, Ph.D., of DRI. We know that genetics affect disease in the Healthy Nevada Project®, and now we are recognizing that ACEs also affect disease, Our new study shows that the combination of genes and environmental factors like ACEs, as well as many social determinants of health, can lead to more serious health outcomes than either variable alone. More broadly, this new work emphasizes how important it is for population genetic studies to consider the impact of social determinants on health outcomes.” Healthy Nevada Project® Principal Investigator Joseph Grzymski, Ph.D., of DRI and Renown Health. The study team believes that it is important for clinical caregivers to understand the strong impact that negative childhood experiences such as ACEs can have on both child and adult health. The researchers hope the information from this study will encourage doctors and nurses to conduct simple screenings for ACEs and consider a patient’s social environment and history in combination with genetics when developing treatment plans for better patient health. According to the 2019 Youth Behavior Risk Survey (YRBS), 25.6 percent of Washoe County teenagers are overweight or obese. Obesity is a serious health concern for children and adolescents. According to the Centers for Disease Control and Prevention, obese children and adolescents are more likely to become obese as adults. Obese and overweight children and adolescents are at risk for multiple health problems during their youth, which are likely to be more severe as adults, Obese and overweight youth are more likely to have risk factors associated with cardiovascular diseases, such as high blood pressure, high cholesterol, and type 2 diabetes. Losing weight, in addition to a healthy diet, helps to prevent and control multiple chronic diseases and improves quality of life for a lifetime.” Max J. Coppes, MD, PhD, MBA, FAAP, Nell J Redfield Chair of Pediatrics at the University of Nevada Reno School of Medicine, Physician in Chief of Renown Children's Hospital. We’d like to thank all of the Healthy Nevada Project® participants who provided information to make our work possible, Our research illustrates that it’s not just genetics that cause disease, but that our environment and life experiences interact with our genes to impact our health in ways that we are only beginning to understand.” Robert Read, M.S., of DRI. About DRI The Desert Research Institute (DRI) is a recognized world leader in basic and applied environmental research. Committed to scientific excellence and integrity, DRI faculty, students who work alongside them, and staff have developed scientific knowledge and innovative technologies in research projects around the globe. Since 1959, DRI’s research has advanced scientific knowledge on topics ranging from humans’ impact on the environment to the environment’s impact on humans. DRI’s impactful science and inspiring solutions support Nevada’s diverse economy, provide science-based educational opportunities, and inform policymakers, business leaders, and community members. With campuses in Las Vegas and Reno, DRI serves as the non-profit research arm of the Nevada System of Higher Education.

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