“We’ve tried to choose diseases for which very, very low doses are going to be required,” says OrbiMed’s Squinto, the firm’s interim CEO. Today, Wilson’s gene therapy center is larger than ever. REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. The FDA can barely keep up with the growing pipeline, and it anticipates receiving more than 200 applications from groups that want to test new cell and gene therapies next year. At the restaurant, his father was explaining the stunning results of a clinical trial underway at UCL that used AAV8. That therapy was approved for sale this May. The goal was to deliver a working copy of the teenager’s broken gene, but the viruses threw his immune system into overdrive. University of Pennsylvania scientist and gene therapy pioneer James Wilson has developed a new tactic designed to make these treatments safer for the nervous system. Why not just transfer the gene instead? Although clinical trials fail all the time, and in fact, other people would die during experimental gene therapy trials, Jesse’s death tapped into fears about the risks of genetic alteration. By submitting your information, you are gaining access to C&EN and subscribing to our weekly newsletter. Those concerns have guided the strategy of Wilson’s new company, Passage Bio, which is focused on rare genetic neurological conditions. “Is it fair for us to avoid developing a potential curative therapy for OTC deficiency because of the past?” The answer, he says, is no. They made it to the movie, Resident Evil, in the nick of time. That same year, a bright student named Luk Vandenberghe joined Wilson’s lab—although other scientists warned him against it. “And that’s what got him in trouble.”. James M. Wilson, MD, PhD, director of the Gene Therapy Program at the University of Pennsylvania, and a co-founder of Passage Bio. Our gene therapy product candidates are designed to deliver genes to cells to address genetic defects or to enable cells in the body to produce therapeutic proteins that are intended to impact disease. High doses also create the additional hurdle of simply manufacturing enough of the viruses for a treatment. James M. Wilson, MD, PhD. A handful of academics with an entrepreneurial bent have turned their biomedical labs into start-up incubators, fueled by troops of precocious graduate students and postdocs. “But Jim’s pretty tough.”, Yamada, meanwhile, had recently left academia to become head of R&D at GlaxoSmithKline. “I sometimes called it the gulag of the Wilson lab,” he jokes. But a few weeks later, the child’s liver enzyme levels skyrocketed. The filing Read the full 241 word article “My motivation was to help patients because of my early experiences as a physician, so that is my driver,” he says. Our Benefits and Perks . Suddenly, all the attention was on Wilson and his lab. Jesse Gelsinger (June 18, 1981 – September 17, 1999) was the first person publicly identified as having died in a clinical trial for gene therapy.Gelsinger suffered from ornithine transcarbamylase deficiency, an X-linked genetic disease of the liver, the symptoms of which include an inability to metabolize ammonia – a byproduct of protein breakdown. On screen, a genetically engineered virus escaped and, of course, turned everyone into zombies. Wilson found himself at the center of multiple investigations. This month, the start-up raised an additional $110 million. Over the next few years, Penn’s viral vector center became the Amazon of AAV. When Gao first presented the data at a lab meeting in mid-December, Wilson was skeptical. The first two they picked, dubbed AAV7 and AAV8, were 10–100 times as good at getting genes into cells as the six previously known viruses. And in April 2018, the Swiss drug giant Novartis agreed to pay $8.7 billion for a company called AveXis, the Nationwide Children’s Hospital spin-off working to commercialize the spinal muscular atrophy therapy, now known as Zolgensma. Both Dr. Wilson and I have been working in the gene therapy field for over 30 years, and this deep understanding will be instrumental as we grow and advance this new world-class gene therapy company… I can't tell you how disappointed I was to find out that nobody credited me with the discovery of all of the 100+ novel AAV vectors, which neither my supervisor, Dr. Gao, nor the head of the lab, Dr. Wilson, could have done without me because I was the only person in the institute who had the scientific expertise and educational background to undertake such an ambitious project using PCR, which was notorious for randomly mutating the DNA, and succeed. Our gene therapy product candidates are designed to deliver genes … The Gelsinger family filed a lawsuit. ), according to an SEC … His work is being applied to genetic treatments by a start-up company, Passage Bio, which has applied for an initial public stock offering (IPO). Before he knew it, 5:00 p.m. had rolled around. Credit: RCSB Protein Data Bank NGL Viewer, PBD ID: 3UX1, The structure of AAV9, a virus discovered in Wilson's lab and later used for the commercial gene therapy Zolgensma. James M. Wilson Gene therapy researcher James Wilson, of the University of Pennsylvania in Philadelphia, directed a clinical trial involving gene therapy that led to the death of 18 … “When I first came to Penn, working with a company was bad, evil,” Wilson says. Wilson’s group never considered that the innate immune system would present an issue, and there was no obvious way to redesign adenoviruses around it. The results of the 15-patient study, published in November 2017, showed that all infants were still alive at 20 months. https://cen.acs.org/.../Gene-therapy-pioneer-James-Wilson/97/web/2019/02 Wilson saw gene therapy as a less extreme option than some contemporary treatments. Some were even able to sit, speak, and walk. For anyone familiar with the slow crawl of drug development, gene therapy is moving at lightning speed. Dr. James Wilson, director of the gene therapy program at the University of Pennsylvania, is taking a new role at a Maryland biotech company he helped launch. “But my passion is science.”. “From Jim’s standpoint, it looked pretty easy,” Yamada says. “These things were being sent out left, right, and center,” Vandenberghe says. He later assumed a lead role at his father’s company Scout Bio, which is developing gene therapies for cats and dogs. “These are intense efforts that normally take place at drug development companies,” explains Vandenberghe, who started his own lab at Massachusetts Eye and Ear in 2012. The largest center of its kind, it was housed at Penn and led by Wilson. “When you are a scientist working here, you feel like nothing is impossible,” she says. But one thing is clear. It was particularly frustrating for a small group of researchers who had been championing the use of a different kind of gene-delivery vehicle: adeno-associated viruses—the AAVs. “The point is to make us walk in the room and remember,” Kakkis says. That and the other protocol violations put all the participants in danger. The glut of money currently flowing in and fueling the establishment of scores of new Gene therapy start-up biotechnology companies virtually overnight like in the Dot Com era combined with the uncertainty of the professional expertise of such companies to responsibly deploy licensed gene therapy vectors in naive patients creates the potential for a Boom-Bust scenario for Gene therapy all over again. It’s an astounding comeback for Wilson’s career and gene therapy in general. James Wilson, M.D., Ph.D. Director of the Gene Therapy Program at the University of Pennsylvania and a co-founder of Scout Bio commented, “I am thrilled that our work in animal models of human diseases … AAVs were first discovered as contaminants of adenovirus samples in 1965. Wilson has expanded his armamentarium to include messenger RNA therapy, which is like a temporary version of gene therapy, as well as gene editing, which can make precise changes to genes instead of replacing them wholesale. In July 2001, a year after the GSK money first arrived, Gao began fishing for new AAVs using a technique called polymerase chain reaction to pull fragments of the viral DNA from monkey tissue. “But we’re working on so many other liver metabolic diseases,” he says. His work is being applied to genetic treatments by a start-up company, Passage Bio, which has applied for an … The company was founded by industry veterans Stephen Squinto, Ph.D., and Tachi Yamada, M.D., in a partnership with gene therapy pioneer James Wilson, M.D., Ph.D, The company has a research, collaboration and license agreement with the University of Pennsylvania and its Gene Therapy Program as well as the Penn Orphan Disease Center. When the results held up, Wilson called the team together on a Saturday in spring 2002 to review the results. The pace is a source of both excitement and anxiety for anyone who’s weathered gene therapy’s peaks and troughs over the past 3 decades. Another site housed the many animals—mice, monkeys, cats, and dogs—in which the experimental AAV gene therapies are tested. With Wilson’s infrastructure and decades of know-how, any spin-off company financed by Squinto’s firm could hit the ground running. His immune system flared up and his organs failed. Matt would often hear about the latest struggles and successes of using viruses to deliver therapeutic genes. “The question is, in the fire and ashes of all of that, can you rise up again and do something to fix the problem?”, Today, Wilson keeps a framed quote in his office next to a photo of himself from his football days. He remained Wilson’s only graduate student for several years. And almost everyone Squinto met was a staff scientist. Despite that—or perhaps because of it—Wilson’s downsized and outcast lab kept plugging away with a newfound focus on finding safer viruses. “It told me that it really was all about the money.”. Annovis Bio is the latest Philly-area biotech firm to sell stock before it has products, PhaseBio raises $120M, buys Selenity; OneDigital buys Tiffany Kistler Benefits; Brightview adds landscapers South and West, PhillyBioCapital: $75M for Limelight ‘leapfrog’ gene therapy; LLR’s $40M to Suvoda. Wilson and others stuffed them into hollowed-out adenoviruses—which are naturally adept at infiltrating cells to propagate their own genes. “At Penn Medicine, we are the most for-profit nonprofit in the world,” Kevin Mahoney, then CEO-elect, told the room. Support for the field overall floundered. As more gene therapies start hitting the market in the coming decade, the university anticipates that it will effectively be printing cash. It was the first public tragedy of a highly hyped field. To top it all off, Amicus also agreed to pay Wilson’s lab $10 million a year for 5 years to expand his work to improve gene therapies and develop the next generation of AAVs. Surgeons were already transplanting whole livers into kids with OTC deficiency to restore that missing enzyme. They went out for a hike in the desert, and Gelsinger recalls that Wilson was going on about his institute, how morale was low after the tragedy, that he was losing people. “Gene therapy was still under the shadow of Jesse Gelsinger,” Gao says. The paperwork for the company made its purpose clear: to commercialize Wilson’s technology. Wilson recently moved his discovery team to a commercial building down the street. He was stripped of his titles, his gene therapy center was disbanded, and he was barred from doing any more clinical trials until 2010. He says it has about 80 open positions, including veterinarians, IND application writers, and even an intellectual property scientist. I am afraid, seriously, that the field is moving too fast. Earlier this year, James Wilson, a gene therapy pioneer, got a call from Luk Vandenberghe, who had been a graduate student in Wilson’s lab two decades ago. You could lose a child.’ ” Wilson backed off. California residents do not sell my data request. Yet Jesse Gelsinger—a man he never met—is an inescapable part of Wilson’s legacy. “I actually thought, believe it or not, that by the time I finished my internship that the problem would be solved,” he says. Gene therapy is conceptually simple: since genetic diseases are caused by faulty genes, giving someone a functional copy of that gene could provide a onetime fix. He told some lawyer friends, Allan Fox and Daniel Kiser, about his dilemma, and they came up to Penn in November 2007, along with their protégé, Ken Mills, to help Wilson figure out how he could get the rights to his viruses back. “Now there is an academic group trying to compete with that, and frankly, service them.” In his estimation, Wilson’s lab has largely become an “IND warehouse.”. We use the information you provide to make your reading experience better, and we will never sell your data to third party members. 125 S. 31st Street, Suite 1200 TRL Philadelphia, PA 19104-3403. PassageBio, started in 2018, is the latest in a two-year wave of dozens of cell and gene therapy start-ups to go public before they have products on the market. The company was founded by industry veterans Stephen Squinto, Ph.D., and Tachi Yamada, M.D., in a partnership with gene therapy pioneer James Wilson, M.D., Ph.D. By continuing to use this site you are agreeing to our COOKIE POLICY. His liver produced low levels of the enzyme. He laid out a plan to convert what remained of his lab into a discovery shop, but he’d need money. Despite their similar names, AAVs are unrelated to the adenoviruses that Wilson used. Jesse Gelsinger (June 18, 1981 – September 17, 1999) was the first person publicly identified as having died in a clinical trial for gene therapy.Gelsinger suffered from ornithine transcarbamylase deficiency, … Money, hard to raise not long ago, is flooding into academic labs and companies developing gene therapies. Copyright © 2020 American Chemical Society. In the course of the afternoon, the team began realizing that they had stumbled upon a new, highly diverse family of AAVs—more than 100 of them. The credit belongs to the man who is actually in the arena, whose face is marred by dust and sweat and blood.”. If you have an ACS member number, please enter it here so we can link this account to your membership. “Now everyone is happy to work with Jim and gives him a lot of money.”. The firm, which employs 20, is developing treatments for rare single-gene disorders of the central nervous system, including Krabbe disease, GM1 gangliosidosis, and frontotemporal dementia. Wilson never met Jesse. BREAKING: Everything we know about the COVID-19 coronavirus. “It is so amazing how his memory has held on and is so alive still,” Gelsinger says. A virus that Gao discovered in 2003 called AAV9 seemed even better. “I basically bullied my way through,” he says. Despite that warning, the company says its goal is to become “the premier genetic medicines company” in collaboration with Penn’s Gene Therapy Program (GTP), which Wilson heads. In fact, it already has. Yet Wilson’s lab stands apart for its scale and for his heavy reliance on more experienced scientists that develop dozens of experimental gene therapies in parallel. The lab’s goal is gathering enough data to support investigational new drug (IND) applications—the documentation that must be submitted to the FDA before beginning clinical trials in humans—for its biotech partners. The investor walked through rows and rows of lab benches—standard biology fare, to be sure, but at an immense scale. Regulatory authorities swept in to investigate the tragedy. Although each experimental gene therapy must be tested anew, it should be relatively straightforward to crank out several more programs that use the same AAV, each just packed with a different gene. They’d begin by further developing gene therapies for five rare neurological diseases. It became a sticking point in the media. Wilson trained only a handful of PhD students at a time. This site uses cookies to enhance your user experience. “And I am willing to pay for it.”. Dr. Wilson has dedicated his career to gene therapy and much of his research has focused on the development of AAV vectors as vehicles for gene delivery. All Rights Reserved. In late November, Wilson flew to Arizona to meet Paul Gelsinger. And his new company, Scout Bio, is developing gene therapies to treat anemia, atopic dermatitis, and chronic pain in pets. Once Penn finished testing the therapies in monkeys, the biotech firm would take the data and petition the US Food and Drug Administration for permission to begin clinical trials in humans. Now that his long ban from running clinical trials had ended, he saw an opportunity to evolve again. Discount will be applied automatically at checkout. Over the next few months, the duo negotiated an intimate arrangement: they would form a new company, and Wilson’s lab at Penn would function as its R&D arm. He runs his gene therapy center like you'd run a very efficient company. That period was a blur of isolating, characterizing, and testing new AAVs, Vandenberghe recalls. James M. Wilson, researcher in gene therapy at the University of Pennsylvania. “I was cheap labor,” he quips. Wilson remembered he had promised to take his 11-year-old son, Matt, to see a sci-fi flick—one that his mom wouldn’t take him to see—and he was running late. “I hate that kind of thing.”. Investor money dried up, and start-ups shuttered. “What has changed significantly is the value that academic institutions place in partnering with industry,” he adds. Gene therapy pioneer James Wilson resigned from the scientific advisory board at Solid Biosciences LLC (Cambridge, Mass. At first, Gelsinger believed Wilson acted in his son’s best interest. Before the OTC deficiency trial began, Wilson’s lab had struggled to control the immune response to the delivery viruses in lab animals. After Jesse Gelsinger’s death, then NIH Director Harold Varmus appointed an ad hoc committee to review NIH policy on gene therapy and recommend if that policy be changed. Choose the membership that is right for you. Password and Confirm password must match. Xconomy National — [Updated, 1/31/18, see below] Gene therapy pioneer James Wilson and University of Pennsylvania colleagues sounded an alarm Tuesday morning about the use of gene therapy … Wilson graduated from Albion College (B.A., Chemistry) and the University of Michigan (MD, PhD). A few years earlier, the university had barred Wilson from interacting with patients because he founded a biotech company called Genovo, which provided funding to the institute that led the clinical trials and held rights to commercialize his discoveries. When Jesse’s body began breaking down within a day of the adenovirus injection, Wilson knew that T cells couldn’t be the culprit, since they take a week or more to mount their attack. Repurposing a proven gene therapy approach to treat, prevent COVID-19 In a Q&A, Penn Medicine’s James M. Wilson discusses using adeno-associated viral vectors to transport a lab-made antibody … Graduate Group Affiliations Cell and Molecular Biology; Contact information. “This is really going to lead to a simplification of the drug development process,” Wilson says. Scientific integrity, vigilance, good clinical practice, responsible oversight, and thorough pre-clinical evaluations are critical to the realization of the promise of gene therapy and the continued success of this field. Business news and analysis sent straight to your inbox every Tuesday morning. “Should we morph to support the industry as it tries to get back on its feet?” Wilson recalls asking his group. To Yamada, the focus on Wilson’s conflict of interest because of Genovo was overblown. 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