Category Archives: Gene Medicine

LEXINGTON, Mass., Dec. 14, 2020 /PRNewswire/ --LogicBio Therapeutics Inc. (Nasdaq: LOGC), a clinical stage genetic medicines company developing therapies based on advanced gene editing technology and next-generation synthetic capsids, today announced that Daphne Karydas and Jeff Goater have been appointed to the Company's board of directors.

"We are excited to welcome Daphne and Jeff. They both bring an impressive depth of experience and proven leadership in the areas of corporate finance, global strategic planning, mergers and acquisitions and strategic partnerships in the biopharma sector," said Frederic Chereau, LogicBio president and CEO. "As we plan for many major developments at LogicBio including initiation of our phase 1/2 SUNRISE clinical trial for LB-001, we believe their expertise will play a central role in guiding our corporate strategic planning and help us reach new levels of momentum in all operational areas."

Ms. Karydas is chief financial officer at Syndax Pharmaceuticals, a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies. Previously, she served as senior vice president of corporate financial planning & analysis and strategy at Allergan plc, where she oversaw financial and business strategy through the company's acquisition by Abbvie in May 2020. Prior to joining Allergan, Ms. Karydas spent over 17 years in asset management and investment banking focused on the bio-pharmaceutical sector. She served as a senior healthcare analyst at J.P. Morgan Asset Management and a portfolio manager and senior healthcare analyst at The Boston Company Asset Management and was a vice president at Goldman Sachs Asset Management and a member of Goldman Sachs' healthcare investment banking team. She began her career as a project chemical engineer at Merck & Co. and earned a B.S. and M.S. in chemical engineering from the Massachusetts Institute of Technology and an M.B.A. from Harvard Business School.

Mr. Goater is chief executive officer at Surface Oncology, an immuno-oncology company developing next-generation antibody therapies. Previously he was chief financial officer of Voyager Therapeutics, helping to guide the company through an initial public offering and establishment of a strategic partnership with Sanofi Genzyme. For almost ten years he was an investment banker, most recently at Evercore Partners where he was an advisor on more than $100 billion in strategic transactions in the biopharma industry. He began his career as a research scientist and earned master's degrees in microbiology/immunology, pathology and business administration from the University of Rochester.

"I am especially excited to be joining the LogicBio board of directors as the Company plans for a range of promising product development milestones and business opportunities based on the potential of the platform," said Ms. Karydas. "I look forward to working with the team to expand the Company's progress and target new opportunities in the rapidly emerging gene editing space."

"In recent years, LogicBio has made significant progress both in advancing its pipeline and in positioning the Company for many promising opportunities in research and business development," said Mr. Goater, adding, "I look forward to joining with the other members of the board in helping the Company achieve its mission of bringing innovative therapies to patients with rare diseases around the world."

"As we welcome Daphne and Jeff to our board, we also are very grateful to Erez Chimovits and Daniel O'Connell, who are stepping down from our board, for their service during several formative and active years for our Company," Mr.Chereau added.

About LogicBio Therapeutics

LogicBio Therapeuticsis dedicated to extending the reach of genetic medicine with pioneering platforms. LogicBio's proprietary genome editing technology platform, GeneRide, enables the site-specific integration of a therapeutic transgene without nucleases or exogenous promoters by harnessing the native process of homologous recombination. LogicBio has received FDA clearance for the first-in-human clinical trial of LB-001, a wholly owned genome editing program leveraging GeneRide for the treatment of methylmalonic acidemia. Patient enrollment in the phase 1/2 SUNRISE clinical trial is expected to begin in early 2021. In addition, LogicBio has a collaboration with Takeda to research and develop LB-301, an investigational therapy leveraging GeneRide for the treatment of the rare pediatric disease Crigler-Najjar syndrome.

LogicBio is also developing a Next Generation Capsid platform for use in gene editing and gene therapies. Data presented have shown that the capsids deliver highly efficient functional transduction of human hepatocytes with improved manufacturability with low levels of pre-existing neutralizing antibodies in human samples. Top-tier capsid candidates from this effort have demonstrated significant improvements over benchmark AAVs currently in clinical development. LogicBio is developing these highly potent vectors for internal development candidates and potentially for business development collaborations.

Forward Looking Statements

This press release contains "forward-looking" statements within the meaning of the federal securities laws. These are not statements of historical facts and are based on management's beliefs and assumptions and on information currently available. They are subject to risks and uncertainties that could cause the actual results and the implementation of the Company's plans to vary materially, including the risks associated with the initiation, cost, timing, progress and results of the Company's current and future research and development activities and preclinical studies and potential future clinical trials. These risks are discussed in the Company's filings with theU.S. Securities and Exchange Commission(SEC), including, without limitation, the Company's Annual Report on Form 10-K filed onMarch 16, 2020, the Company's Quarterly Report on Form 10-Q filed on May 11, 2020, and the Company's subsequent filings with theSEC. Except as required by law, the Company assumes no obligation to update these forward-looking statements publicly, even if new information becomes available in the future.

Media contact:Jenna UrbanBerry & Company Public Relationsjurban@berrypr.com212 253 8881

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SOURCE LogicBio Therapeutics, Inc.

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LogicBio Therapeutics names Daphne Karydas and Jeff Goater to Board of Directors - BioSpace

Reston, Va.; December 17, 2020The Society is pleased to announce and recognize the 2021 SOT Award recipients for their many accomplishments and their commitment to the field of toxicology. The 2021 awardees represent outstanding researchers in academia, industry, and government across the globe and career stages. The work of these awardees has improved human, animal, and environmental health and addresses diverse areas, such as environmental health disparities of underserved populations, toxicokinetics of xenobiotics, and reducing animal use in toxicity testing.

This yearmore than any year in the immediate pasthas illustrated the importance of scientists working to advance public health. The SOT Award recipients represent those at the forefront of basic, translational, and cutting-edge research aimed at benefiting public health, says George P. Daston, PhD, 20202021 SOT President. The SOT Awards also honor individuals who are training the next generation of scientists and the fields most promising postdoctoral and student researchers.

SOT also is proud to welcome two new Honorary members in 2021:

The 2021 SOT Award recipients and new Honorary members will be honored during the Societys Virtual 2021 Annual Meeting and ToxExpo, March 1226, 2021.

SOT AWARDS**conferred by the SOT Awards Committee

SOT Achievement Award

SOT Arnold J. Lehman Award

SOT Distinguished Toxicology Scholar Award

SOT Education Award

SOT Enhancement of Animal Welfare Award

SOT Founders Award (for Outstanding Leadership in Toxicology)

SOT Leading Edge in Basic Science Award

SOT Merit Award

SOT Public Communications Award

SOT Toxicologist Mentoring Award

SOT Translational Impact Award

SOT Undergraduate Educator Award

SUPPORTED AWARDS

Colgate-Palmolive Awards for Student Research Training in Alternative Methods

Colgate-Palmolive Grants for Alternative Research

Colgate-Palmolive Postdoctoral Fellowship Award in In Vitro Toxicology

Syngenta Fellowship Award in Human Health Applications of New Technologies

ADDITIONAL AWARDS

Toxicological Sciences Paper of the Year Award

SOT Best Postdoctoral Publication Awards

SOT Perry J. Gehring Diversity Student Travel Award

SOT Undergraduate Research Awards

More information on the 2021 Award recipients is available on the SOT website.

# # #

About SOT Awards and HonorsThe Society of Toxicology (SOT) Awards program recognizes distinguished toxicologists and students each year based on merit. In 1962, the Society inducted its first Honorary members, establishing its honors program. In 1965, the SOT Awards program was created with the establishment of two awards, the SOT Merit Award and the SOT Achievement Award, to support the furtherance of the science of toxicology. Today, the Society presents more than 20 awards that recognize achievement, facilitate travel for senior and budding scientists, and further toxicological research. Hashtag: #SOTAwards

About SOTFounded in 1961, the Society of Toxicology (SOT) is a professional and scholarly organization of more than 8,000 scientists from academic institutions, government, and industry representing the great variety of individuals who practice toxicology. SOT is committed to creating a safer and healthier world by advancing the science and increasing the impact of toxicology. The Society promotes the acquisition and utilization of knowledge in toxicology, aids in the protection of public health, and has a strong commitment to education in toxicology and to the recruitment of students and new members into the profession. SOT values diversity, equity, and inclusiveness in all their forms and promotes them as part of all Society activities. For more information about SOT, visit the Societys website or like/follow SOT on Facebook, Instagram, LinkedIn, and Twitter.

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Scientists Advancing Public Health Research Honored with 2021 Society of Toxicology Awards - Newswise

TORONTO--(BUSINESS WIRE)--Vasomune Therapeutics, Inc., a clinical-stage biopharmaceutical company, announced today the first subjects have been dosed in a Phase 1 study of AV-001 in healthy subjects. AV-001 is a first-in-class therapeutic that targets the Tie2 tyrosine kinase receptor, a key regulatory protein in the vasculature responsible for maintaining normal vascular function. Should the benefit demonstrated in animal studies translate to the clinic, AV-001 has the potential to improve survival and shorten the duration of hospitalization for patients hospitalized with COVID-19.

Emerging evidence suggests serious SARS-CoV-2 infection impairs vascular function in the lungs and throughout the body, which explains why patients with pre-existing vascular dysfunction (elderly, hypertension, diabetes and obesity) are at higher risk. Our therapeutic strategy focuses on normalizing the vasculature, which we believe could improve patient survival and shorten recovery time, which, in turn, would reduce the strain on healthcare resources, including medical personnel, ICU beds and ventilators, said Douglas Hamilton, President and CEO of Vasomune.

The Phase 1 randomized, double-blind, placebo-controlled single and multiple ascending dose trial of AV-001 is currently enrolling healthy subjects. This study is a first-in-human design to assess the safety, tolerability and pharmacokinetics of daily administration of single and multiple doses of AV-001. Vasomune Therapeutics, Inc. plans to seek Emergency Use Authorization (EUA) from the US Food and Drug Administration (FDA) pending successful clinical trials for the treatment of patients with moderate-to-severe COVID-19 disease.

About AV-001

Originally discovered and designed at Sunnybrook Hospital in Toronto, AV-001 is being developed by Vasomune Therapeutics, Inc. under a co-development agreement with AnGes, Inc. [TYO: 4563]. AV-001 is a novel investigational medicine that targets the Tie2 receptor, a transmembrane protein target most highly expressed on the surface of endothelial cells in the vasculature. AV-001 activates the Tie2-Angiopoietin pathway and restores normal vascular function and endothelial stability. Vascular dysfunction contributes to the underlying disease pathophysiology in patients with COVID-19 and acute respiratory distress syndrome (ARDS), especially in patients with pre-existing vascular comorbidities, such as hypertension, diabetes and obesity. Emerging evidence suggests SARS-CoV-2 infects pulmonary endothelial cells and causes microvascular leaks, contributing to the initiation and propagation of respiratory distress and ARDS in COVID-19 patients by altering blood vessel barrier integrity, promoting a coagulated state and inducing vascular inflammation (endotheliitis). In preclinical studies involving a lethal RNA virus infection animal model of influenza/ARDS, AV-001 has been shown to stabilize the vasculature by enhancing endothelial cell stability, restoring normal barrier defense and blocking vascular leak. Importantly, AV-001 monotherapy significantly improved survival and lung function compared to untreated controls and showed the benefit of enhanced recovery in combination with antiviral therapy. AV-001 is being developed for the treatment of moderate to-severe COVID-19 and ARDS.

About Vasomune Therapeutics, Inc.

Vasomune Therapeutics, Inc. is a private clinical-stage biopharmaceutical company developing the next generation of medicines to harness the bodys ability to defend against illness. Originally founded in 2014, Vasomune discovers and develops drugs using a novel therapeutic approach focused on vascular normalization strategies. Vascular dysfunction is associated with the pathology of several disease states, including COVID-19, influenza-associated ARDS, acute lung injury, acute kidney injury, hemorrhagic shock, sepsis and stroke. Vasomunes corporate headquarters and laboratory is located in Toronto, Canada with US offices in San Mateo, CA. For more information about the company and its product candidates, please visit http://www.vasomune.com.

About AnGes, Inc.

AnGes, Inc., a biopharmaceutical company founded in December 1999, focuses on the development of gene-based medicines. In March 2019, AnGes obtained conditional and time-limited approval for its lead product, Collategene (Hepatocyte Growth Factor, HGF, plasmid gene therapy), for the treatment of lower limb ischemic ulcers. In September 2019, AnGes commenced the commercialization in Japan of Collategene. Collategene is the worlds first marketed drug using plasmid DNA. AnGes is currently focusing on the development of DNA vaccines for COVID-19 and hypertension, a Tie2 tyrosine kinase receptor agonist for COVID-19 treatment and an NF-B decoy oligonucleotide for chronic discogenic lumbar back pain. Furthermore, AnGes acquired EmendoBio in December 2020 to expand its capabilities in genome-editing technologies. For more information, visit https://www.anges.co.jp/en/.

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Vasomune Therapeutics Announces Initiation of the First-in-Human Clinical Trial of a Potential Vascular Normalization COVID-19 Treatment - Business...

Scientists at Washington University School of Medicine (WUSM) in St. Louis have spent some years investigating the links between circadian rhythm and Alzheimers, and have recently been making some real inroads. Following a 2018 study demonstrating how disrupted sleep can accelerate the buildup of toxic plaques associated with the disease, the team has now identified a protein implicated in the progression of the disease that appears highly regulated by the circadian rhythm, helping them join the dots and providing a potential new therapeutic target.

In their previous research, the WUSM team set out to explore how disruptions to our natural sleep cycles, or circadian rhythm, may accelerate the accumulation of amyloid plaques in the brain, which are strongly linked to Alzheimers disease. Through studies on humans and in mice, the team was able to show a strong correlation between the two, and now through follow up work, the team has identified a brain protein that appears to play a role in this relationship.

The brain protein in question is called YKL-40 and for years has served as a biomarker for Alzheimers, as high levels of it have been found in the cerebrospinal fluid of those suffering from the disease and these levels rise as the disease progresses. The researchers were screening for genes that are regulated by the circadian rhythm, and were intrigued to see the gene for this brain protein pop up.

The gene for YKL-40 came up as highly regulated by clock genes, says Erik Musiek, senior author. That was really interesting because it is a well-known biomarker for Alzheimers.

From there, the team investigated this connection between YKL-40 and Alzheimers, which is characterized by chronic inflammation, by exploring how much of the protein is made under inflammatory conditions both with and without a key circadian gene. Indeed, this demonstrated that the circadian rhythm controls how much YKL-40 is produced.

If you have inflammation in the morning, you might get lots of YKL-40; if you get inflammation in the evening, when the clocks in a different phase, you might get less YKL-40, Musiek says.

Next up, the team worked with mice prone to developing amyloid plaques, and genetically modified one group of them to be lacking the gene for YKL-40. As the mice reached old age, the team analyzed their brains and found that those without the YKL-40 protein exhibited around half the amyloid plaques of the control group.

Digging deeper into the reasons why, the team found that the mice lacking the YKL-40 gene featured more microglia, which are immune cells that surround amyloid plaques and prevent them from spreading. Essentially, this meant that those mice had more hungry immune cells prepared to gobble up the amyloid.

This YKL-40 protein probably serves as a modulator of the level of microglial activation in the brain, Musiek says. When you get rid of the protein, it appears the microglia are more activated to eat up the amyloid. Its a subtle thing, a tweak in the system, but it seems to be enough to substantially reduce the total amyloid burden.

The team also examined this idea in human subjects, drawing on genetic data on 778 subjects from aging and dementia studies and finding only a quarter of them featured a genetic variant that lowers levels of YKL-40, and that cognitive function declined 16 percent more slowly in that group.

If your circadian clock is not quite right for years and years you routinely suffer from disrupted sleep at night and napping during the day the cumulative effect of chronic dysregulation could influence inflammatory pathways such that you accumulate more amyloid plaques, says Musiek. We hope that a better understanding of how the circadian clock affects YKL-40 could lead to a new strategy for reducing amyloid in the brain.

The research was published in the journal Science Translational Medicine.

Source: Washington University School of Medicine in St. Louis

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Biomarker of Alzheimer's found to be regulated by sleep cycles - New Atlas

A single protein that appears necessary for the COVID-19 virus to reproduce and spread to other cells is a potential weakness that could be targeted by future therapies.

The molecule, known as transmembrane protein 41 B (TMEM41B), is believed to help shape the fatty outer membrane that protects the virus genetic material while it replicates inside an infected cell and before it infects another.

The latest finding comes from a pair of studies led by researchers at NYU Grossman School of Medicine and NYU Langone Healths Perlmutter Cancer Center, and colleagues at Rockefeller University and elsewhere.

Published in the journal Cell online December 8, 2020, the studies revealed that TMEM41B was essential for SARS-CoV-2 to replicate. In a series of experiments, researchers compared how the COVID-19 virus reproduces in infected cells to the same processes in two dozen deadly flaviviruses, including those responsible for yellow fever, West Nile, and Zika disease. They also compared how it reproduces in infected cells to three other seasonal coronaviruses known to cause the common cold.

Together, our studies represent the first evidence of transmembrane protein 41 B as a critical factor for infection by flaviviruses and, remarkably, for coronaviruses, such as SARS-CoV-2, as well, says the studies co-senior investigator John T. Poirier, PhD.

An important first step in confronting a new contagion like COVID-19 is to map the molecular landscape to see what possible targets you have to fight it, says Poirier, an assistant professor of medicine at NYU Langone Health. Comparing a newly discovered virus to other known viruses can reveal shared liabilities, which we hope serve as a catalog of potential vulnerabilities for future outbreaks.

While inhibiting transmembrane protein 41 B is currently a top contender for future therapies to stop coronavirus infection, our results identified over a hundred other proteins that could also be investigated as potential drug targets, says Poirier, who also serves as director of the Preclinical Therapeutics Program at NYU Langone and Perlmutter Cancer Center.

For the studies, researchers used the gene-editing tool CRISPR to inactivate each of more than 19,000 genes in human cells infected with each virus, including SARS-CoV-2. They then compared the molecular effects of each shutdown on the virus ability to replicate.

In addition to TMEM41B, some 127 other molecular features were found to be shared among SARS-CoV-2 and other coronaviruses. These included common biological reactions, or pathways, involved in cell growth, cell-to-cell communication, and means by which cells bind to other cells. However, researchers say, TMEM41B was the only molecular feature that stood out among both families of viruses studied.

Interestingly, Poirier notes, mutations, or alterations, in TMEM41B are known to be common in one in five East Asians, but not in Europeans or Africans. He cautions, however, that it is too early to tell if this explains the relatively disproportionate severity of COVID-19 illness among some populations in the United States and elsewhere. Another study finding was that cells with these mutations were more than 50 percent less susceptible to flavivirus infection than those with no gene mutation.

Poirier says more research is needed to determine if TMEM41B mutations directly confer protection against COVID-19 and if East Asians with the mutation are less vulnerable to the disease.

The research team next plans to map out TMEM41Bs precise role in SARS-CoV-2 replication so they can start testing treatment candidates that may block it. The team also has plans to study the other common pathways for similar potential drug targets.

Poirier adds that the research teams success in using CRISPR to map the molecular weaknesses in SARS-CoV-2 serves as a model for scientists worldwide for confronting future viral outbreaks.

References:

TMEM41B IS A PAN-FLAVIVIRUS HOST FACTOR by H.-Heinrich Hoffmann, William M. Schneider, Kathryn Rozen-Gagnon, Linde A. Miles, Felix Schuster, Brandon Razooky, Eliana Jacobson, Xianfang Wu, Soon Yi, Charles M. Rudin, Margaret R. MacDonald, Laura K. McMullan, John T. Poirier and Charles M. Rice, 8 December 2020, Cell.DOI: 10.1016/j.cell.2020.12.005

Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks by William M. Schneider, Joseph M. Luna, H.-Heinrich Hoffmann, Francisco J. Sanchez-Rivera, Andrew A. Leal, Alison W. Ashbrook, Jeremie Le Pen, Inna Ricardo-Lax, Eleftherios Michailidis, Avery Peace, Ansgar F. Stenzel, Scott W. Lowe, Margaret R. MacDonald, Charles M. Rice and John T. Poirier, 9 December 2020, Cell.DOI: 10.1016/j.cell.2020.12.006

Study funding was provided by National Institutes of Health grants R01 AI091707, U19 AI111825, R01 CA190261, R01 CA213448, U01 CA2133359, R01 AI143295, R01 AI150275, R01 AI124690, R01 AI116943, P01 AI138938, P30 CA008748, P30 CA016087, R03 AI141855, R21 AI142010, T32 CA160001. Additional funding support was provided by the G. Harold and Leila Y. Mathers Charitable Foundation, the BAWD Foundation, and Fast Grants.

Besides Poirier, another NYU Langone researcher involved in these studies is Andrew Leal. Other collaborators included study co-senior investigator Charles Rice and study co-investigators William Schneider, Joseph Luna, Heinrich Hoffman, Alison Ashbrook, Jeremie Le Pen, Inna Ricardo-Lax, Eleftherios Michailidis, Avery Peace, Ansgar Stenzel, Margaret MacDonald, Kathryn Rozen-Gagnon, Felix Schuster, Brandon Razooky, Eliana Jacobson, Xianfang Wu, and Soon Yi, at Rockefeller University in New York City; Francisco-Sanchez-Rivera, Scott Lowe, Linda Miles, and Charles Rudin, at Memorial Sloan Kettering Cancer Center in New York City; and Laura McMullen, at the U.S. Centers for Disease Control and Prevention in Atlanta.

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Potential Weakness in SARS-CoV-2 Discovered Single Protein Needed for COVID-19 Virus to Reproduce and Spread - SciTechDaily

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Nearly 40 patients with a genetic disease that rapidly blinds young adults were successfully treated with gene therapy, according to a paper published today in Science Translational Medicine. The study was conducted by an international team coordinated by Dr. Jos-Alain Sahel from the University of Pittsburgh and Institut de la Vision, Paris, and Dr. Patrick Yu-Wai-Man from the University of Cambridge.

Dr. Jos-Alain Sahel

Surprisingly, scientists found that injecting a gene therapy vector into one eye of someone suffering from Leber hereditary optic neuropathy (LHON) the most common cause of blindness caused by dysfunctional mitochondria in cells of the retina significantly improved vision in both eyes.

LHON is a rapidly progressing genetic disease that causes optic nerve damage and develops in early adulthood. Within a few weeks of disease onset, the vision of most people affected deteriorates to the point where they are considered legally blind.

As someone who treats these young patients, I get very frustrated about the lack of effective therapies, said Sahel, senior investigator of the study and professor and chair of the Department of Ophthalmology at Pitt School of Medicine, as well as director of the UPMC Eye Center. These patients rapidly lose vision in the course of a few weeks to a couple of months. Our study provides a big hope for treating this blinding disease in young adults.

In their effort to correct a genetic error in the mitochondrial DNA a mutation in the gene called MT-ND4 researchers injected an artificial virus containing a template for the correct copy of the gene into the eyes of 37 patients.

We expected vision to improve only in the eyes treated with the gene therapy vector, said international coordinating investigator and neuro-ophthalmologist Yu-Wai-Man, from Cambridges Department of Clinical Neurosciences. Rather unexpectedly, both eyes improved for 78% of patients in the trial following the same trajectory over two years of follow-up.

On average, the best possible vision in treated and untreated eyes improved by three lines of vision 15 and 13 letters on the worldwide standard eye testing chart, respectively. In some patients, the effect was even larger, reaching 28.5 letters for the treated eyes and 24.5 letters for untreated eyes.

To better understand the mechanism by which the treatment of one eye could improve the other, the researchers conducted a study in long-tailed macaques. Macaques have a visual system similar to that of humans, which allows scientists to study the distribution and effects of the gene therapy vector in much greater detail.

The animal study suggested that the gene therapy can reach an untreated eye by passive diffusion traces of the viral vectors genetic material were detected in the back of the untreated eye, including retina and optic nerve.

Our approach isnt just limited to vision restoration, said Sahel. Other mitochondrial diseases could be treated using the same technology.

The technology, called mitochondrial targeting, was developed by the Institut de la Vision in Paris and licensed to GenSight Biologics, a biotech company co-founded by Sahel. The company is seeking marketing authorization from the European Medicines Agency to use its technology as treatment for patients with visual loss due to LHON caused by a confirmed mutation in the ND4 mitochondrial gene.

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Gene Therapy Injection in One Eye Surprises Scientists by Improving Vision in Both - UPMC