Three Philadelphia scientists won a $3 million Breakthrough Prize for developing the first FDA-approved gene therapy for a genetic disease, prize sponsors announced Saturday.
Their work created a scientific and regulatory road map for gene therapies, paving the way for more than a dozen similar approvals to follow.
The awardees — Jean Bennett, Katherine High, and Albert Maguire — were receiving the award on Saturday evening at a ceremony in Los Angeles known as the “Oscars of Science.”
Bennett, 71, and Maguire, 66, are married and emeritus professors at the University of Pennsylvania. High, 74, is CEO of RhyGaze, a company based in Switzerland and Philadelphia that is developing gene therapies for vision disorders.
Their one-time therapy, called Luxturna, was approved by the Food and Drug Administration in 2017 to treat inherited retinal diseases caused by mutations in a gene called RPE65, notably Leber congenital amaurosis. The genetic disease causes degeneration of the retina, a layer of cells within the eye that detects light.
This leads to severe vision loss or blindness over time.
By delivering a functional copy of the affected gene to patients’ eyes, the scientists found they could improve vision.
The annual international set of awards, founded in 2012 by tech giants to recognize major scientific advances, honored the Philadelphia trio’s yearslong collaboration.
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Bennett brought expertise in molecular biology. Maguire, an ophthalmic surgeon, knew how to deliver treatment into the eye. And High, then researching hemophilia at Children’s Hospital of Philadelphia and Penn, knew how to advance a research discovery through clinical trials to reach patients.
Their discovery not only has advanced treatment for retinal disorders, but also “charts the path” for new gene therapies, said Huda Zoghbi, chair of the selection committee for the Breakthrough Prize in Life Sciences.
“You needed the three of them,” she said.
Luxturna does not completely restore vision, but it can change patients’ lives by reversing some vision loss and slowing the progression of the disease.
Its approval helped bolster the reputation of Spark Therapeutics, which spun out of CHOP in 2013, as a pioneering gene therapy company, and establish Philadelphia as a biotech hub.
Today, about 15 gene therapy products have FDA approval to treat genetic disease, according to High.
Bennett recalls how patients and families described the therapy changing their lives at an FDA open session meeting when Luxturna was seeking regulatory approvals.
“It still makes me well up with tears thinking about some of the stories people told,” said Bennett, who described herself as “thrilled and honored, and humbled,” to share the prize.
The idea
Bennett met Maguire while dissecting a brain together as students at Harvard Medical School.
She was interested in applying her Ph.D. in zoology and cell and developmental biology to treat disease at its genetic origins, a concept not yet tested in humans.
He had become interested in the retina, an area of the eye that he compared to a camera film that converts light into pictures via signals to the brain.
Knowing that many retinal diseases are genetic, Maguire thought cloning a functional copy of a gene and putting it into the affected tissue could treat defects.
He asked Bennett, “You think we could do it?” She said, “Yes.“
At the time, few genes for the retinal diseases had even been identified.
Starting in the early 1990s, they spent about a decade developing all of the technical aspects of their therapy, including figuring out how to deliver the gene and measure its function.
“It was good that we didn’t know how difficult it would be,” Bennett said.
They ultimately focused on diseases caused by mutations in the RPE65 gene, including some forms of Leber congenital amaurosis, a condition where children can generally see only incredibly bright light at birth.
Their limited vision disappears over time, as cells degenerate and die.
The duo designed their therapy using what is called a “vector,” which functions much like a delivery truck carrying packages.
In their case, their vector was a “gutted” virus designed to carry a functional copy of the mutated RPE65 gene, Maguire said.
Using a needle the diameter of three strands of hair, they could inject their therapy directly into the eye.
In the late 1990s, they learned collaborators had obtained dogs with the same mutated gene that humans with the disease had.
Four of the puppies were available for their study. In July 2000, they injected the therapy into one eye each in three of the dogs, and left a fourth as an untreated control for comparison.
Within a week, they received a call from their collaborators.
The dogs were running around without bumping into things, “which they couldn’t do beforehand,” Bennett said. They were even stealing kibble from other dogs who couldn’t see the food bowl nearly as well.
“It was really a eureka moment,” Bennett said.
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The collaboration
As High’s first trials on a gene therapy for hemophilia were starting to show success, a patient’s death in a separate gene therapy trial at Penn roiled the field.
Jesse Gelsinger’s death in 1999, the first from a gene therapy clinical trial, coupled with the development of leukemia in several patients participating in separate trials, scared investors away from gene therapy, to the point that the California-based company High relied on to manufacture her vectors could not raise money.
“All the news about gene therapy was bad. Didn’t matter whether you were reading scientific journals or the Wall Street Journal,” High said.
High explained her dilemma to Steven Altschuler, who was the CEO of CHOP at the time. If they couldn’t start producing those vectors in the hospital, she was going to have to stop her gene therapy research.
A week later, he said he would find the resources for vector production in the hospital — but under one condition.
High had to work on other diseases that affect the pediatric population, not just hemophilia.
Her mind quickly went to Bennett, a longtime colleague. Their children were even in school together.
High asked Bennett if she would be interested in moving her “great dog results” into humans.
A landmark approval
By 2007, the team of Bennett, High, and Maguire started their clinical trial, initially with three adult patients.
Early safety data persuaded regulators to let them include children, who stood to benefit the most, given the disease’s degenerative nature.
It was the first time children who did not have a fatal disease were involved in gene therapy trials, High noted.
By 2012, the team had launched a pivotal, phase 3 trial. To measure the effects, they developed a mobility test to measure “functional vision” in daily living.
It consisted of a mobility course, which had a series of guiding arrows on the floor and obstacles like steps and a door.
The researchers measured the lowest light level at which patients could get a passing score.
They found that patients in the intervention group were able to pass the course at lower light levels, with a quicker pace, and maintain that progress over a year.
In 2017, they received approval from the Food and Drug Administration for the therapy marketed as Luxturna.
It works for patients with mutations in the RPE65 gene, which accounts for around 5% to 10% of Leber congenital amaurosis cases.
Luxturna’s impact
Today, most of the roughly 1,000 people estimated to be eligible in the U.S. have been treated, and the therapy has since moved into overseas markets.
Though a scientific success, it has not performed well commercially.
Luxturna was listed at $425,000 per eye when it was approved. Swiss pharmaceutical giant Roche assumed ownership of the one-time therapy in 2019 after acquiring Spark Therapeutics.
In 2025, sales were about $50 million.
That has not stopped others from trying to enter the space.
Dozens of retinal gene therapy trials targeting different conditions are underway worldwide.
Luxturna is “a breakthrough because it was really the first to do that all the way,” Zoghbi said.