Category Archives: Gene Medicine

image:For mice placed in chronic jet lag (CJL) conditions, they showed a 68% increase in tumor burden when compared to mice placed in 12 hours of light, 12 hours of darkness (12:12 LD). view more

Credit: Scripps Research

LA JOLLA, CADisruptions in circadian rhythmthe ways that our bodies change in response to the 24-hour light and dark cyclehave been linked to many different diseases, including cancer. The connection between the two has been poorly understood, even though shift workers and others with irregular schedules experience these disruptions regularly. But a new discovery from Scripps Research is helping answer what may be behind this correlation.

Published in Science Advances on September 28, 2022, the findings highlight that chronic circadian disruption significantly increased lung cancer growth in animal models. By identifying the genes implicated, the researchers are illuminating the mysterious link between our sleeping patterns and disease, which could help inform everything from developing more targeted cancer treatments to better monitoring high-risk groups.

There has always been a lot of evidence that shift workers and others with disrupted sleep schedules have higher rates of cancer, and our mission for this study was to figure out why, says senior author Katja Lamia, PhD, associate professor in the Department of Molecular Medicine.

To answer this question, the scientists used a mouse model with expressed KRAS the most commonly mutated gene in lung cancer. Half of the mice were housed in a normal light cycle, meaning 12 hours of light and 12 hours of darkness. The other half were housed in a light cycle meant to resemble that of shift workers, where the light hours were moved earlier by eight hours every two or three days.

The findings aligned with what the researchers initially thought: mice that were exposed to the irregular, shifting light patterns had an increased tumor burden of 68%.

But when they used RNA sequencing to determine the different genes involved in the cancer growth, they were surprised that a collection in the heat shock factor 1 (HSF1) family of proteins was the main culprit.

This is not the mechanism we were expecting to find here. HSF1 has been shown to increase rates of tumor formation in several different models of cancer, but it has never been linked to circadian disruption before, Lamia says.

HSF1 genes are responsible for making sure proteins are still made correctly even when a cell is under extreme stressin this case, when it experiences changes in temperature. The team suspects that HSF1 activity is increased in response to circadian disruption because changes in our sleep cycles disturb the daily rhythms of our bodies temperature.

Normally, our body temperature changes by one or two degrees while were sleeping. If shift workers dont experience that normal drop, it could interfere with how the HSF1 pathway normally operatesand ultimately lead to more dysregulation in the body, Lamia adds. She believes cancer cells may exploit the HSF1 pathway to their own benefit and create mutant, misfolded proteins, but says more research is needed in this area.

These findings help shape not only our understanding of how circadian rhythms impact cancer, but also potentially a preventative way of protecting more vulnerable groups who are at risk. By non-invasive monitoring of body temperature, it may be possible to optimize shift workers schedules and even halt this type of dysregulation that can lead to cancer.

With these discoveries in hand, the scientists are now evaluating if HSF1 signaling is required to increase tumor burden and isnt solely just a correlation.

Now that we know theres a molecular link between HSF1, circadian disruption and tumor growth, its our job to determine how theyre all connected, Lamia says.

In addition to Lamia, authors of the study, Circadian disruption enhances HSF1 signaling and tumorigenesis in Kras-driven lung cancer, include Marie Pariollaud, Lara H. Ibrahim, Emanuel Irizarry, Rebecca M. Mello, Alanna B. Chan, Michael J. Bollong and R. Luke Wiseman of Scripps Research; Brian J. Altman of University of Rochester Medical Center; and Reuben J. Shaw of Salk Institute.

Funding for this research was provided by the National Institutes of Health grant CA211187 (KAL), Brown Foundation for Cancer Research (KAL), National Institutes of Health grant DK107604 (RLW), National Institutes of Health grant R00CA204593 (BJA) and National Science Foundation/DBI-1759544 (EI).

About Scripps Research

Scripps Research is an independent, nonprofit biomedical institute ranked the most influential in the world for its impact on innovation by Nature Index. We are advancing human health through profound discoveries that address pressing medical concerns around the globe. Our drug discovery and development division, Calibr, works hand-in-hand with scientists across disciplines to bring new medicines to patients as quickly and efficiently as possible, while teams at Scripps Research Translational Institute harness genomics, digital medicine and cutting-edge informatics to understand individual health and render more effective healthcare. Scripps Research also trains the next generation of leading scientists at our Skaggs Graduate School, consistently named among the top 10 US programs for chemistry and biological sciences. Learn more atwww.scripps.edu.

Circadian disruption enhances HSF1 signaling and tumorigenesis in Kras-driven lung cancer

28-Sep-2022

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The surprising link between circadian disruption and cancer may have to do with temperature - EurekAlert

ReportLinker

MARKET INSIGHTS Live cell imaging is one of the popular techniques for studying live cells and investigating the biological processes in real-time. It utilizes time-lapse microscopy and careful preparation of living cell environments that have made it easier to observe cell-to-cell interactions and study the behavior of single cells and related changes within the cell.

New York, Sept. 28, 2022 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Live Cell Imaging Market - Global Outlook & Forecast Market 2022-2027" - https://www.reportlinker.com/p06323431/?utm_source=GNW In 2021, North America accounted for the highest share of the global live cell imaging market.

Live cell imaging has revolutionized studying cells, processes, and molecular interactions. Imaging techniques for living cells allow scientists to study cell structures and processes in real-time and over time. Such factors have significantly impacted the growth of the market. A few of the most widespread applications include examining the structural components of a cell, the dynamic studying processes, and the localization of molecules.

MARKET TRENDS & DRIVERS

Rising Target Patient Population

Live cell imaging is a vital tool in the study of cancer biology. Although high-resolution imaging is indispensable for studying genetic and cell signaling changes in underlying cancer, live cell imaging is essential for a deeper understanding of the function and disease mechanisms. Around 400,000 children develop cancer every year. Developed and emerging countries are facing the burden of communicable diseases. Most developing countries get exposed due to several factors that include demographic, socio-economic, and geographic conditions. Hence, the growing number of deaths and chronic conditions drive the live cell imaging market.

Deep Learning & Artificial Intelligence

The role of Artificial intelligence (AI) in life science is rapidly expanding and holds great potential for microscopy. In the past, the power of microscopy for supporting or disproving scientific hypotheses got limited by scale, and the time associated with quantifying, capturing, and analyzing large numbers of images was often prohibitive. Recently, AI has made fast inroads into many scientific fields and the world of microscopy. AI-based self-learning microscopy shows the potential to produce high throughput image analysis that is more effortless and less time-consuming. Newer AI technology allows better visualization of unlabeled live cells over a prolonged period.

Increase in Funding for Cell & Gene Therapy

The demand for regenerative medicine has increased across developed countries, and investments in cell & gene therapy have grown drastically in recent years. The public and private sectors are at the forefront of funding cell and gene therapy developers. Recently, many government organizations and private firms have started funding many biotech start-ups and research institutes that invest in the R&D of cell and gene therapy products. According to the Alliance for Regenerative Medicines, there was a 164% jump in funding for cell & gene therapy in 2019 compared to 2017.

Advancements & Newer Imaging Techniques

Live cell imaging arises from scientific interest coupled with imaging and labeling technology improvements. Putting together various technological advancements with biological interests gives scientists many more ways to use live cell imaging. In particular, exciting progress in probe development has enabled a broad array of nucleic acids, proteins, glycans, lipids, ions, metabolites, and other targets to be labeled. Many recent advancements in microscopic technologies use software that enables a better quantitative image analysis of label-free images.

Also, current microscopy techniques limit the quantity and quality of information available to researchers and clinicians and harm the living cells during long-term studies. Hence new imaging technologies are being developed to overcome various limitations. These advancements will help towards future market growth. For instance, the progress of combining 3D fluorescence imaging and holotomography microscopy has overcome some limitations.

Growing Research-based Activities

In the past two decades, the spending on R&D and the introduction of newer drugs have increased rapidly. In 2019, the pharma industry spent around $83 billion on R&D. From 2010 to 2019, the number of novel drugs were approved, whose sales increased by 60% compared with the previous decade, with a peak of 59 new drugs approved in 2018. The rising amount of R&D expenditure and the number of R&D activities in the pharmaceutical sector has led to the significant growth of the market.

SEGMENTATION ANALYSIS

The global live cell imaging market by product includes sub-segments by equipment, consumables, and software. In 2021, the equipment sector accounted for the highest share in the global live cell imaging market.Under the equipment sector, live-cell imaging microscopes are opening novel and exciting avenues for studying cellular health, viability, colony formation, migration, and cellular responses to external stimuli. The demand for microscopes is at a larger scale, majorly due to the technological advancements in microscopes and increasing studies into cell behavior. Fluorescence microscopy, confocal microscopy, transmitted light microscopy, and other techniques are included in the global live cell imaging market by technique. Fluorescence microscopy held the largest share of 53.68% in the global live cell imaging market in 2021. Live-cell imaging techniques are involved in a wide spectrum of imaging modalities, including widefield fluorescence, confocal, multiphoton, total internal reflection, FRET, lifetime imaging, super-resolution, and transmitted light microscopy. An increasing number of investigations are using live-cell imaging techniques. Owing to these advances, live-cell imaging has become a requisite analytical tool in most cell biology laboratories. Cell biology, drug discovery, developmental biology, and stem cell are the applications primary segments of the live cell imaging market. In 2021, cell biology accounted for the highest share of 38.72% in the global live cell imaging market. The end-user market includes segments by pharma & biotech companies, academic & research institutes, and others. Academic and research institutions identify promising discoveries and seek to initiate their development and commercialization. Most new insights into biology, disease, and new technologies arise in academia, funded by public grants, foundations, and institutional funds. The discovery and development of new therapies have and will likely continue to require contributions from academic institutions and the biopharmaceutical industry.

Segmentation by Product Type Equipment Consumables Software

Segmentation by Technique Fluorescence microscopy Confocal microscopy Transmitted light microscopy Others

Segmentation by Application Cell Biology Drug Discovery Developmental Biology Stem Cells

Segmentation by End-Users Pharma & Biotech Companies Academic & research centers Others

GEOGRAPHIC ANALYSIS

By geography, the report includes North America, Europe, APAC, Latin America, and the Middle East & Africa. In 2021, North America accounted for the highest share of the global live cell imaging market.

Live cell imaging systems are used for diagnostics purposes, drug discovery & development, and precision medicine. The increase in healthcare expenditures and funding for R&D activities for live cells-driven drug discovery, development, and personalized medicine is one of the major driving factors for leading the North American region. Europe holds the second-largest share of the global market, owing to a growing patient population in need of new treatments such as stem cell therapy and gene therapy, an increasing number of drug approvals for precision medicine, government funding for research-based activities, rapid advancements in live cell imaging, and a variety of other factors.

The APAC region will likely witness the fastest growth in the global live cell imaging market. The significant factors behind this growth can be due to the constant rise in cancers and infectious diseases, growing demand for stem cell research studies, rising R&D expenditures, the increased utility of biomarkers for diagnostic purposes, rising awareness for cell & gene therapies, need for precision medicine, and advances in drug discovery & cell and biology development. However, Latin America and Middle East & Africa accounted for minimal shares in the global market.

Segmentation by Geography

North Americao THE USo Canada Europeo Germanyo Franceo UKo Italyo Spain APACo Japano Chinao Indiao South Koreao Australia Latin Americao Brazilo Mexicoo Argentina Middle East & Africao Turkeyo Saudi Arabiao South Africao UAE

COMPETITIVE LANDSCAPE

The leading players in the market are implementing various strategies such as marketing and promotional activities, mergers & acquisitions, product launches, and approvals. Also, high R&D investments and boosting distribution networks have helped companies enhance their market share and presence.

The global live cell imaging market includes global and regional players. Major players contributing to the markets significant shares include Agilent, Bruker, Carl Zeiss AG, Danaher, Merck KGaA, PerkinElmer, and Thermo Fisher Scientific. Other prominent players in the market include Axion (CytoSMART Technologies), Bio-Rad Laboratories, blue-ray biotech, Etaluma, Grace Bio Labs, ibidi GmbH, KEYENCE, NanoEnTek, Nanolive SA, Nikon, Olympus, and others.

Recent Developments in the Global Market

In 2021, CytoSMART launched CytoSMART Lux3 BR, a new type of bright-field microscope, i.e., a live-cell imaging microscope equipped with a high-quality CMOS camera to assist label-free cell imaging procedures. In 2021, the Zeiss group announced that they would launch Zeiss Visioner 1, a Zeiss live cell imaging system, an innovative digital microscope that facilitates real-time all-in-one focus via a micro-mirror array system. In 2020, CytoSMART Technologies launched CytoSMART Multi Lux, a remote live cell imaging system.

Key Vendors Danaher Agilent Technologies PerkinElmer Merck KGaA ZEISS Thermo Fisher Scientific

Other Prominent Vendors Axion BioSystems BD Bio-Rad Laboratories Blue-Ray Biotech Bruker Eppendorf Etaluma Grace Bio-Labs ibidi GmbH Intelligent Imaging Innovations KEYENCE Logos Biosystems NanoEntek Nanolive SA Nikon Evident ONI Oxford Instruments Phase Focus Phase Holographic Imaging PHI AB Proteintech Group Sartorius AG Sony Biotechnology Tomocube

KEY QUESTIONS ANSWERED1. What is the expected live cell imaging market size by 2027?2. What is the live cell imaging market growth?3. What are the latest trends in the live cell imaging market?4. Who are the market leaders in the global live cell imaging market?5. Which region has the largest live cell imaging market share?Read the full report: https://www.reportlinker.com/p06323431/?utm_source=GNW

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The global live cell imaging market is expected to grow at a CAGR of 8.44% during 2022-2027 - Yahoo Finance

Members Bradley Bernstein, M.D., Ph.D., Paula Cannon, Ph.D., Howard Chang, M.D., Ph.D., and Ahmad (Mo) Khalil, Ph.D., will guide advancement of the company's epigenetic editing platform and key programs

Scientific Advisors join Chroma Founders, Luke Gilbert, Ph.D., Keith Joung M.D., Ph.D., David Liu, Ph.D., Angelo Lombardo, Ph.D., Luigi Naldini, M.D., Ph.D., and Jonathan Weissman, Ph.D., expanding the company's world-class team of leaders in genomic medicine

CAMBRIDGE, Mass., Sept 20, 2022 /PRNewswire/ -- Chroma Medicine, Inc., (Chroma) a genomic medicine company pioneering single-dose epigenetic editing therapeutics, today announced the formation of a Scientific Advisory Board (SAB) comprising renowned leaders in epigenetics, cell and gene therapy, and synthetic biology: Bradley Bernstein, M.D., Ph.D., Paula Cannon, Ph.D., Howard Chang, M.D., Ph.D., and Ahmad (Mo) Khalil, Ph.D. The SAB members will provide key input to Chroma as the company advances its programs addressing a wide range of diseases.

"Each of these distinguished experts will be instrumental as we unlock the potential of epigenetic editing therapeutics," said Catherine Stehman-Breen, M.D., Chief Executive Officer of Chroma Medicine. "We are honored to welcome them to the Chroma team and eager to leverage their expertise as we build the future of genomic medicine."

"The SAB is composed of scientific leaders whose seminal research has significantly advanced the fields of genome editing and cell and gene therapy," said Vic Myer, Ph.D., President and Chief Scientific Officer of Chroma. "They bring a wealth of knowledge and experience to Chroma as we continue to advance our platform with the goal of bringing novel single-dose genomic therapeutics to patients."

Members of the Chroma Scientific Advisory Board include:

About Chroma Medicine

Chroma Medicine is a biotechnology company pioneering a new class of genomic medicines that harness epigenetics, nature's innate mechanism for gene regulation, to deliver single-dose therapeutics for patients with genetically driven diseases. The company was founded by the world's foremost experts in genomic research and is led by a veteran team of industry leaders and scientists with deep experience in genomic medicine, drug discovery, and development. For more information, please visit chromamedicine.com or follow the company on LinkedIn and Twitter.

SOURCE Chroma Medicine

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Chroma Medicine Announces Formation of Scientific Advisory Board of Global Experts in Gene Editing and Cell and Gene Therapy - PR Newswire

Ring Therapeutics

CAMBRIDGE, Mass., Sept. 20, 2022 (GLOBE NEWSWIRE) -- Ring Therapeutics, a life sciences company founded by Flagship Pioneering to revolutionize gene therapy with its commensal virome platform, today announced the issuance of U.S. Patent No. 11,446,344. The patent, which was granted to Flagship Pioneering, is exclusively licensed to Ring Therapeutics.

The patent covers anellovirus vectors, which can be used to deliver a diversity of therapeutic modalities. This patent builds on a previous patent (U.S. Pat. No. 11,166,996) granted in November 2021 on methods of delivering a therapeutic polypeptide or nucleic acid by administering Anellovector compositions.

"Ring has comprehensively pioneered a new class of viral vector by generating scientific understanding of anelloviruses through our research work and publications, said Tuyen Ong, MD, MBA, Chief Executive Officer of Ring Therapeutics. This patent issuance supports the novelty of the Anellogy platform and our unique approach of harnessing the human commensal virome to engineer life-saving therapies, ultimately redefining what is possible in programable medicine.

Avak Kahvejian, Ph.D., General Partner of Flagship Pioneering and Co-Founder and Chairman of Ring added, This is another example of Flagship Pioneering companies conducting science at the frontiers of human biology to develop new solutions for humanity. Rings conception of Anellovectors as a broad bioplatform that could be applicable across diseases holds tremendous promise for unlocking the field of genetic medicines.

About Ring Therapeutics

Ring Therapeutics is revolutionizing the gene therapy and nucleic acid medicine space by harnessing the most abundant and diverse member of the human commensal virome, anelloviruses. The company developed the Anellogy platform which focuses on anelloviruses to potentially treat a broad range of diseases. Through harnessing the unique properties of these commensal viruses, the Anellogy platform generates diverse vectors that exhibit both tissue-specific tropism and the potential to be redosed. Founded by Flagship Pioneering in 2017, Ring Therapeutics aims to develop and further expand its portfolio through leveraging its platform to unlock the full potential of gene therapy and nucleic acid medicines, enabling a variety of mechanisms that successfully deliver therapeutic cargo to unreachable organs and tissues. To learn more, visithttps://ringtx.com or follow us on Twitter at@Ring_tx.

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Ring Therapeutics Media:Brittany Leigh, Ph.D.LifeSci Communicationsbleigh@lifescicomms.com+1-813-767-7801

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Ring Therapeutics Announces Issuance of U.S. Patent for its Anellovector Compositions - Yahoo Finance

An unexplained case of severe coronary artery disease in a seemingly healthy young man led scientists at The Ohio State University Wexner Medical Center and College of Medicine to a discovery that could lead to a new way to treat high cholesterol.

Ohio State scientists discovered rare genetic mutations that had never been identified before, and that could cause severe early onset of coronary artery disease, the most common type of heart disease in the United States. The discovery is leading to a better understanding of how cholesterol functions and the possibility of developing safer therapeutics for the 94 million Americans with high cholesterol.

Marcus Wright, of Delaware, Ohio, was 27 when he suffered a heart attack and continued to have heart-related problems. Doctors were puzzled after finding out he had severe coronary artery disease despite being active and eating a healthy diet.

He was eventually referred to Dr. Ernest Mazzaferri, Jr., an interventional cardiologist at Ohio States Richard M. Ross Heart Hospital and a clinical professor of Internal Medicine.

When I met Marcus about 14 years ago, he looked like a linebacker for the Ohio State Buckeyes. He was super fit and active. He was the last guy that you would ever think would have this kind of disease, said Mazzaferri, co-interim director of Ohio States Heart and Vascular Center. His cholesterol and inflammation numbers looked pretty good and there was no family history of heart disease at that point, so it didn't make sense why somebody like him would have such advanced disease.

Despite optimal medical therapy, Wright continued to have symptoms and needed multiple heart stents, which are expandable metal coils placed in a blocked blood vessel to keep the arteries open.

When both Wrights mother and younger brother were later diagnosed with severe coronary artery disease, Mazzaferri suspected there was a genetic link. He decided it would be a good case for Ohio States JB Project, which is funded by philanthropy and brings together clinicians and scientists to decipher the root cause of highly unusual cases involving coronary artery disease, arrhythmias and heart failure.

Marcus became the first patient I ever presented to our genetic scientists and I said, 'Nobody can figure out what's wrong with this young man. I need your help to understand what's wrong with him,'" said Mazzaferri, who holds the Charles A. Bush, MD Professorship in Cardiovascular Surgery.

A team of researchers led by Sara Koenig, assistant professor of Internal Medicine, conducted genetic sequencing of Wrights DNA and identified unique genetic variants that were causing his advanced disease. To better understand the potential implications of these genetic mutations, Koenig expanded her study, identifying the same mutations in his mother, father and brothers.

This gene encodes a receptor for HDL, which is classically referred to as your good cholesterol, Koenig said. We hypothesize that good cholesterol does not function as well in these individuals as the general population.

The researchers determined that Wrights genetic variants prevented his good cholesterol from effectively clearing out his bad cholesterol (known as LDL), leading to his advanced coronary artery disease. Their findings were published in the American Heart Associations Circulation Research.

The identification of these specific variants in Marcus and his family and knowing that they are causing coronary artery disease sheds lights on a new pathway that we can approach for cholesterol mediated therapy, Koenig said.

Researchers examined 788 FDA drugs approved for various diseases to narrow down which ones may promote a healthy HDL function. They are now working on developing different diagnostic tests and a new therapeutic drug that may provide an alternative option for those living with high cholesterol.

Genetics play a really important role in cholesterol and cardiovascular disease. Even if youre doing everything right by exercising and eating the right foods, some people are just predisposed to high cholesterol and coronary artery disease, which is exactly what happened to Marcus, Koenig said. The issue with statins, which lower your cholesterol, is that theyre not 100% effective. Weve identified a handful of drugs that promote the good HDL pathway or reverse cholesterol transport. Now we are investigating these drugs in animal and human cell models in the hope that we can identify how they affect the pathway and develop more targeted therapies.

Over the years, Mazzaferri has made changes to Wrights medications and now only sees him once a year.

We do the things we do with the hope that we're going to be able to impact people's lives, and to have a group like the JB project work together over a couple year period to really solve a problem like this was one of the most memorable things I'll ever have in my career, Mazzaferri said.

Knowing what was causing his heart problems and learning he probably didnt pass the genetic mutations along to his three children was a relief for Wright.

It was a relief because you're like Okay, now somebody knows something instead of just being a medical mystery, Wright said. They're saying the likelihood is I wouldn't pass it on. As a father, that's the biggest thing that you could be concerned with. I know my parents didn't want to give it to me, and this shouldnt be one of those things that my kids have to worry about.

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Cholesterol gene mutation: Why would a healthy 27-year-old have severe heart problems? - 69News WFMZ-TV

An analysis found that a single dose of gene therapy would be more cost-effective than on-demand or prophylaxis factor replacement in 92% of cases.

Hemophilia is a hereditary, lifelong, and life-threatening disorder that, until recently, has had no prospective cure. Gene therapy might change that, but the cost has been predicted to be in the millions.

Individuals with hemophilia have a gene mutation that causes a deficiency in one of two factors integral in the blood coagulation pathway. In hemophilia A, factor XIII is missing; in hemophilia B, its factor IX. Hallmark symptoms of the disease include excessive bleeding after internal or external trauma. Areas particularly affected are joints, muscles, and soft tissues. In severe cases, bleeding can occur spontaneously.

Current therapy for hemophilia consists of on-demand or prophylactic intravenous infusions of replacement clotting factor to treat or prevent bleeding. Prophylaxis therapy requires several infusions per week, and the cost can range from $300,000 to $776,000 per year.

Recent research on gene therapy introduces the possibility to significantly reduce or eliminate the need for factor replacement therapy. Treatment is designed as a one-time intravenous injection consisting of an adeno-associated virus vector carrying instructions for liver cells to produce deficient coagulation factors.

At least three gene therapies for hemophilia B are currently in late-stage clinical trials, and all have demonstrated at least a 90% reduction in bleeding events and the need for factor replacement. If all goes well, gene therapy can be a potential cure for hemophilia, but the cost has been estimated at $2 to $3 million per patient.

St. Jude Childrens Research Hospital conducted a cost-effectiveness analysis of gene therapy for severe hemophilia B and found that the novel treatment may be more cost-effective than current therapy despite its sky-high price tag. In the analysis, published in the journal Blood last November, St. Jude used its own hospitals data to compare the cost and cost effectiveness of gene therapy with on-demand and prophylaxis factor replacement therapy.

Researchers calculated a total per-patient cost of $87,198 for the manufacturing, distribution, and five-year follow-up of gene therapy for severe hemophilia B. Taking into account the cost of lifelong factor replacement therapy, bleeding complications during on-demand treatments, orthopedic surgery, and hospitalizations, the analysis found that a single dose of gene therapy would be more cost-effective than on-demand or prophylaxis factor replacement in 92% of cases.

According to the authors, gene therapy is in a unique position when it comes to cost analysis. Nancy Bolous, M.D., from St. Jude Global Pediatric Medicine and lead author of the analysis, said, Gene therapy is different because unlike other treatment approaches, it is a long-lasting, one-time treatment and may require a big upfront payment, a payment that can make the affordability seem questionable. Our analysis importance is that it sheds light on the many factors that could play a role in the decision-making process regarding reimbursement.

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Gene Therapy for Severe Hemophilia B Could Be More Cost Effective Than Current Treatments - Managed Healthcare Executive

CAMBRIDGE, Mass.--(BUSINESS WIRE)--AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company working to free people from a lifetime of genetic disease, today announced that the U.S. Food and Drug Administration (FDA) has granted rare pediatric disease designation to AVR-RD-04, an investigational gene therapy for the treatment of cystinosis, a life-threatening disease that causes progressive multi-organ damage, including early, acute kidney disease progressing to end-stage kidney disease.

FDAs Rare Pediatric Disease Designation and Voucher Program is intended to facilitate the development of new drugs and biologics for the prevention and treatment of rare pediatric diseases. Companies that receive approval for a New Drug Application (NDA) or Biologics License Application (BLA) for a rare pediatric disease may be eligible to receive a voucher for a priority review of a subsequent marketing application for a different product. The priority review voucher may be used by the company or sold to a third party.

AVR-RD-04 is designed to genetically modify patients own hematopoietic stem cells (HSCs) to express the gene encoding cystinosin, the protein that is critically deficient in people living with cystinosis.

Preliminary data from the ongoing University of California San Diego Phase 1/2 clinical trial suggest that this approach is well tolerated, with no adverse events (AEs) related to the drug product reported to date. All AEs reported were related to myeloablative conditioning, stem cell mobilization, underlying disease or pre-existing conditions. The majority of AEs were mild or moderate and resolved without clinical sequelae. Clinical data to date indicate this investigational approach provides benefits in multiple tissues evaluated, including the eyes, skin, gastrointestinal mucosa and the neurocognitive system. The collaborator-sponsored Phase 1/2 clinical trial is funded in part by grants to University of California San Diego from the California Institute for Regenerative Medicine (CIRM), Cystinosis Research Foundation (CRF) and National Institutes of Health (NIH).

About CystinosisCystinosis is a rare, progressive disease that impacts approximately 1,600 patients in the U.S., Europe and Japan and is marked by the accumulation of cystine in cellular organelles known as lysosomes. Untreated cystinosis is fatal at an early age. The current SOC for cystinosis, a treatment regimen that can require dozens of pills per day, does not prevent overall disease progression and carries side effects, such as breath and body odor and gastrointestinal symptoms, which can impede compliance. More than 90% of treated cystinosis patients require a kidney transplant in the second or third decade of life.

About AVROBIOOur vision is to bring personalized gene therapy to the world. We target the root cause of genetic disease by introducing a functional copy of the affected gene into patients own hematopoietic stem cells (HSCs), with the goal to durably express the therapeutic protein throughout the body, including the central nervous system. Our first-in-class pipeline includes clinical programs for cystinosis and Gaucher disease type 1, as well as preclinical programs for Gaucher disease type 3, Hunter syndrome and Pompe disease. Our proprietary plato gene therapy platform is designed to be scaled to support late-stage clinical development and commercialization globally. We are headquartered in Cambridge, Mass. For additional information, visit avrobio.com, and follow us on Twitter and LinkedIn.

Forward-Looking StatementsThis press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words and phrases such as aims, anticipates, believes, could, designed to, estimates, expects, forecasts, goal, intends, may, plans, possible, potential, seeks, will, and variations of these words and phrases or similar expressions that are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our preclinical and clinical product candidates, including AVR-RD-04 for the treatment of cystinosis, the potential benefits and incentives provided by FDAs rare pediatric disease designation for AVR-RD-04, the design, commencement, enrollment and timing of planned clinical trials, preclinical or clinical trial results, product approvals and regulatory pathways, our plans and expectations with respect to interactions with regulatory agencies, anticipated benefits of our gene therapy platform including potential impact on our commercialization activities, timing and likelihood of success, the expected benefits and results of our implementation of the plato platform in our clinical trials and gene therapy programs, and the expected safety profile of our preclinical and investigational gene therapies. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be indicative of results from later stage or larger scale clinical trials and do not ensure regulatory approval. You should not place undue reliance on these statements, or the scientific data presented.

Any forward-looking statements in this press release are based on AVROBIOs current expectations, estimates and projections about our industry as well as managements current beliefs and expectations of future events only as of today 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 such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that any one or more of AVROBIOs product candidates will not be successfully developed or commercialized, the risk of cessation or delay of any ongoing or planned clinical trials of AVROBIO or our collaborators, the risk that AVROBIO may not successfully recruit or enroll a sufficient number of patients for our clinical trials, the risk that AVROBIO may not realize the intended benefits of our gene therapy platform, including the features of our plato platform, the risk that our product candidates or procedures in connection with the administration thereof will not have the safety or efficacy profile that we anticipate, the risk that prior results, such as signals of safety, activity or durability of effect, including beneficial effects seen in multiple organs and tissues, observed from preclinical or clinical trials, will not be replicated or will not continue in ongoing or future studies or trials involving AVROBIOs product candidates, the risk that we will be unable to obtain and maintain regulatory approval for our product candidates, the risk that the size and growth potential of the market for our product candidates will not materialize as expected, risks associated with our dependence on third-party suppliers and manufacturers, risks regarding the accuracy of our estimates of expenses and future revenue, risks relating to our capital requirements and needs for additional financing, risks relating to clinical trial and business interruptions resulting from the COVID-19 outbreak or similar public health crises, including that such interruptions may materially delay our enrollment and development timelines and/or increase our development costs or that data collection efforts may be impaired or otherwise impacted by such crises, and risks relating to our ability to obtain and maintain intellectual property protection for our product candidates. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause AVROBIOs actual results to differ materially and adversely from those contained in the forward-looking statements, see the section entitled Risk Factors in AVROBIOs most recent Annual or Quarterly Report, as well as discussions of potential risks, uncertainties and other important factors in AVROBIOs subsequent filings with the Securities and Exchange Commission. AVROBIO explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.

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AVROBIO Receives Rare Pediatric Disease Designation from U.S. Food and Drug Administration (FDA) for First Gene Therapy in Development for Cystinosis...

The relatively short history of cell and gene therapy is not lacking in dramatic moments. A previous outlier, this vibrant field now represents the next great hope and so, when roadblocks to progress are removed or even lowered, theres reason to celebrate. Here, seven members of The Medicine Maker Power List 2022, reflect on the most impactful cell and gene milestones.

There have been many significant breakthroughs in cell and gene therapy over the past few years. Specifically in gene-modified cell therapy, the CAR T story is remarkable. Over the past several years, multiple autologous CAR T therapies have been successfully translated from bench to bedside and received marketing authorization as potentially curative therapies for patients with recalcitrant cancer indications: Kymriah and Yescarta for treating r/r/ ALL, MCL, and LBCL, and Abecma for treating r/r multiple myeloma.

Equally impressive in gene therapy, Zolgensma, an AAVSMN1 gene replacement product, has been developed for use as a one-time gene replacement treatment for infants with spinal muscular atrophy (SMA). The 15 year follow-up study these tiny patients are enrolled in after treatment will inform us on the long-term safety and efficacy of gene replacement therapy.

These products have been translated by academia and SMEs and partnered for advanced development with pharma to achieve both medical and commercial success.

The biggest breakthrough is our increasing ability to edit genes with a growing number of new classes of gene editing tools. This advance has led to the boom of CAR T products and is opening the path to cell engineering and in vivo gene therapy.

In parallel, we are seeing an evolution from viral delivery to alternatives with growing payload capacity. This will, as we are already seeing, lead to cures in diseases where that was unthinkable before!

Cell and gene therapies are at the forefront of innovation and transforming how we treat and potentially cure certain diseases. Cell and gene therapies(CGTs) have the potential to treat severe diseases, such as cancer, as well as rare diseases. Several such therapies are now on the market, including a treatment for an inherited retinal disease that causes blindness. That particular CGT represents an important medical milestone because it was the first curative gene therapy approved for use. Personally, I was excited and humbled at the same time to have been the Global Head bringing this transformational therapy to patients around the world. Many other CGTs are now in development and hopefully will lead to an expansion of the still-limited treatment options available to many patients and transform the clinical paradigm.

An important breakthrough? The demonstration that gain-of-function genetically weaponized somatic cells are potent pharmaceuticals in their own right: living synthetic therapeutics (LSTs).Case in point, after a quarter century of work with TILs and LAKs struggling to meet utilitarian endpoints, enter gain-of-function CAR engineering, and thus history is made.The same paradigm of cell gain-of-function genetic enhancement can readily be applied to alternate somatic cell platforms think MSCs and iPSCs with a limitless potential to improve clinical outcomes for acute and chronic ailments.

Id like to emphasize three milestones. First, the commercialization of gene therapies in general. The efficacy and safety have improved a lot since the 1990s.

Secondly, the explosion of immunotherapies. Onco-hematology has become a major opportunity for patients with otherwise lethal blood cancers.

Finally, the advances in gene editing technologies. These have opened the door to new therapies which we would have considered utterly incredible a few years ago.

The recent approval for Yescarta in second-line (2L) relapsed/refractory large B-cell lymphoma (LBCL) means that an order-of-magnitude more patients just became eligible for potentially curative therapies. One recent industry insight from Celltelligence suggested that moving from 3L to 2L will potentially double the targetable population in diffuse LBCL alone for CAR T cell therapy. As cell therapies move up the treatment paradigm and cell-based therapeutics are eventually approved to treat a range of cancers, the spotlight will turn (again) to manufacturing capacity. At Cellares, our belief is that high-throughput, end-to-end automation is set to revolutionize cell therapy manufacturing, allowing us to deliver more doses at lower cost to meet the demand. Its a truly exciting time for our industry!

The success of the CAR T cell therapy approach and how it has led to cures for childhood leukemias and lymphomas is an amazing story. Thanks to these incredible advances, kids who would no longer be here today are now effectively cured, and are going to live long, relatively healthy lives without suffering the long-term side effects of traditional chemotherapy and radiation. By allowing investigators to be highly creative in developing this approach, a fascinating new treatment process was developed, for both autologous and allogeneic CAR T cell therapies. Now, an entire industry has been born from utilizing patients and donors stem cells and a modified version of the AIDS virus to cure leukemia. This is truly a mind-blowing advancement that combines so many complex processes and biologics and really showcases the power of creative investigators to come up with amazing new treatment solutions.

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The Biggest CGT Breakthroughs Through the Eyes of Our 2022 Power List - The Medicine Maker

The School of Medicine has named Mariano A. Garcia-Blanco, MD, PhD, as the next chair of its Department of Microbiology, Immunology and Cancer Biology

The School of Medicine has recruited Mariano A. Garcia-Blanco, MD, PhD, an internationally recognized expert in virology and RNA biology, to lead its Department of Microbiology, Immunology and Cancer Biology.

Dr. Garcia-Blanco is a nationally recognized researcher in helping the scientific community better understand gene expression in viruses, and he combines that knowledge with deep experience as both an educator and the leader of a department, said Melina R. Kibbe, MD, the dean of the UVA School of Medicine and chief health affairs officer for UVA Health.Together with this skills and background, he has a clear vision for a department that is conducting cutting-edge research of vital importance.

Garcia-Blanco comes to UVA from the University of Texas Medical Branch, where he has served as chair of the Department of Biochemistry and Molecular Biology since September 2014. A founder of five biotechnology companies and holder of over 11 patents, Garcia-Blanco is a member of the United Nations Council of Scientific Advisers for the International Centre for Genetic Engineering and Biotechnology, and he has previously been a member of the National Institutes of Healths National Advisory General Medical Sciences Council. He has also been elected to the Association of American Physicians and named a fellow of the American Association for the Advancement of Science, the American Academy of Microbiology, and the American Academy of Arts and Sciences.

Continuously funded by the NIH since the early 1990s, Dr. Garcia-Blanco has co-authored more than 190 peer-reviewed scientific publications. His research has focused on how the interactions between proteins and RNA regulate gene expression in cells and viruses. His projects have ranged from examining ways to dial the immune system down in autoimmune diseases and up in cancer to identifying new targets to treat diseases caused by flaviviruses, such as yellow fever, Zika and West Nile. His work has also shed important light on multiple sclerosis and other autoimmune disorders.

As an educator, Dr. Garcia-Blanco has been educating undergraduate, graduate and medical students on topics such as gene regulation, nucleic acids, cancer biology, and autoimmunity, among others.He has mentored over 20 doctoral students and 40 postdoctoral fellows throughout his career and fostered the career development of countless junior faculty.Along with his research and teaching at the University of Texas Medical Branch, he is an adjunct professor of emerging infectious diseases at Duke-NUS Medical School in Singapore. Before coming to Texas, Garcia-Blanco was a faculty member at Duke University from 1990 to 2014.

Our excellent faculty in the Department of Microbiology, Immunology and Cancer Biology will benefit greatly from Dr. Garcia-Blancos inclusive, servant leadership, Kibbe said.I also look forward to seeing how his research continues to help the world better understand both fundamental biology and human disease.

Garcia-Blanco earned his bachelors degree from Harvard University and his MD and PhD from Yale University. He also completed a fellowship at Massachusetts Institute of Technology before joining Duke University.

I am thrilled to be joining the Department of Microbiology, Immunology and Cancer Biology, the School of Medicine, and the University of Virginia, and honored to work with them to achieve excellence in biomedical sciences for the common good, Garcia-Blanco said.

He succeeds Amy Bouton, PhD, who had served as interim chair of the Department since October 1, 2021. Her commitment and dedication to the department has been clear to all and very much appreciated.

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Leading Virus Researcher to Chair UVA's Department of Microbiology, Immunology and Cancer Biology - UVA Health Newsroom

In 1976, a letter to the editor thanked this publication for its coverage of the genetic disease Tay-Sachs, and for regularly promoting opportunities to get tested.

At the time, Tay-Sachs remained a scourge in the Jewish community. Since then, in a victory of community willpower over genetic destiny, a concerted push for early testing has virtually eradicated the disease reducing the number of Ashkenazi children born with Tay-Sachs from 60 per year, to 3 to 5 per year.

But while the incidence of Tay-Sachs among Ashkenazi Jews has fallen, a host of genetic disorders still threatens the community, necessitating genetic screening.

We need to plan and be proactive about it, said Estie Rose, a genetic counselor with JScreen, an Atlanta-based nonprofit that offers testing and education.

In 2008, the U.S. Senate named September Tay-Sachs Awareness Month, but Tay-Sachs is only one of the genetic diseases for which Ashkenazi Jews are more likely to carry a recessive gene. (A recessive gene, as opposed to a dominant one, is expressed only when inherited from both parents.)

According to Rose, about 75 percent of those with Ashkenazi Jewish heritage carry a recessive gene for at least one of a number of genetic conditions. Besides Tay-Sachs, the most common include Gaucher disease, cystic fibrosis, familial dysautonomia and Canavan disease. (According to the Jewish Genetic Disease Consortium, there are also various genetic diseases that are more prevalent among Sephardic Jews.) One in 30 Ashkenazi Jews carries the gene for Tay-Sachs, while among the general population, 1 in 300 is a carrier (the number is also high among those of Cajun descent).

While a recessive gene does no harm, a child with Tay-Sachs is more likely to be born to a couple who are both Ashkenazi Jews.

Its really only a problem if the person youre having a child with has the same gene, explained Mary Norton, an MD and professor of perinatal medicine and genetics at the University of California, San Francisco.

The reason Ashkenazi people are more likely to carry the Tay-Sachs gene is interwoven with the many calamities in the history of the Jewish people. Think the Crusades; think the Holocaust; think the Spanish Inquisition, Rose said. The size of the community shrunk, then it regrew.

For genetics, such circumstances exemplify a population bottleneck and the founder effect. In laypersons terms: Many Jews were killed at various times in history, leaving a smaller pool of genes to replenish the population. Also, Jews in Europe were endogamous, meaning they tended to marry other Jews.

The mutations become copy and pasted over and over and over again, Rose said.

Tay-Sachs was discovered toward the end of the 19th century, and even back then its prevalence among Ashkenazi Jews was noted.

The most common form becomes noticeable in infants around 6 months old. Symptoms include reduced vision and an exaggerated startle response, and then progress to slow growth, listlessness, neural degeneration and seizures by age 2, with death coming by age 5. The disease has no cure.

A carrier of a genetic disorder may have no family history of the disease or have the disease themselves. Pregnancy is often the first time many people get tested to see if they are carriers for a range of genetic disorders. Some dont get tested at all.

JScreens mission is to encourage people not to wait until pregnancy to get tested.

Thats what Rose did, and it changed her life. While in college, she and her partner got tested to see which genetic disorders they carried. It turned out they were both carriers for cystic fibrosis, a life-threatening disease. If shed had children with her then-partner, they could have faced some tough choices.

We decided to break up and avoid all of those things, she said.

Today, as a genetic counselor, Rose helps couples consider their options when faced with similar scenarios. She said JScreen tests for 225 diseases and works closely with the primary health care provider and genetic counselors.

I can serve my own community, which is really important to me, she said. The Jewish community unfortunately faces a lot of genetic health issues.

About 75 percent of those with Ashkenazi Jewish heritage carry a recessive gene for at least one of a number of genetic conditions.

Rose said if a pregnant couple finds they both carry the same disease gene, the next step is to test the fetus. If the fetus has the disorder, the couple has to choose whether or not to carry the baby to term. Even better is to do the testing before pregnancy, Rose said: In case there is a problem, they have more options.

The couple can explore IVF (in which each embryo can be tested before implantation) or egg donation, or they may decide not to have children or even go their separate ways, as Rose and her then-partner did.

Sophia Pesotchinsky is all in favor of testing before pregnancy. Her daughter Vera, 49, has Late Onset Tay-Sachs, a rare form of the disease.

The Pesotchinskys came to the Bay Area from Russia in 1976. Vera later developed motor function problems that turned out to be the first signs of LOTS. Sophia had never been tested to see if she was a carrier, neither in Russia nor here in the U.S. when she was considering having more children. Thats a huge oversight, she said.

If people have come from a different country, they have to be asked, Did you have that test? she said.

Thats particularly true for people who come from the former Soviet Union. Very often they didnt know they had Jewish roots, she pointed out.

Sophia said it took more than a decade to diagnose Vera (along the way, Sophia was told that her daughters problems, ranging from slurring to klutziness, came from having an overbearing immigrant mother). Vera, who earned an MBA from Santa Clara University and a BA from Wellesley College, is currently in a wheelchair and cannot live alone, but mother and daughter are active in patient advocacy through the National Tay-Sachs and Allied Diseases Association.

JScreen isnt the only Jewish organization trying to get people to screen early.

New York-based Dor Yeshorim screens potential couples in the Orthodox community by running tests for over 50 diseases. According to their most recent quarterly report, of more than 9,000 people who have used the service, 120 were found to be genetically incompatible.

Like JScreen, Dor Yeshorim advises people to get tested well before pregnancy. When a match is suggested its time for a compatibility check. Dor Yeshorim, rabbanim and experienced shadchanim urge everyone to check compatibility before a couple or the parents meet to avoid unnecessary heartache! the site says.

To that end, Dor Yeshorim often tests at Orthodox schools. JScreen works with Hillel and Birthright, Rose said.

Advances mean that genetic tests once reserved for Ashkenazi Jews can now be accessed by the population at large, further reducing the likelihood that children will be born with a disease like Tay-Sachs.

Tests used to cover only 25 or so gene disorders, but now hundreds can be identified.

Rose said its important to test no matter what ethnicity you are. While Ashkenazi Jews have their own set of risks, other ethnic groups have theirs. You never know what a test result will bring, Rose noted.

We all have things we dont know about our family history, she said.

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Work remains on Tay-Sachs and other Ashkenazi genetic disorders J. - The Jewish News of Northern California