Late last year, dozens of researchers spanning thousands of miles came together to form race to save one boy's life. The result is a world first: a cutting-edge gene editing therapy designed for one person and manufactured in record six months.
Now baby KJ Muldoon's doctors are preparing to do it all again, at least five times. And faster.
Groundbreaking clinical trial described October 31 in the journal American Journal of Human Geneticslet's unfold an offshoot of the CRISPR-Cas9 gene editing technique called base editing.which allows scientists make precise single-letter changes to DNA sequences. The study is expected to begin next year after its organizers spent months negotiating with U.S. regulators about ways to streamline the convoluted path that gene-editing therapies typically take before they can enter trials.
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Developing KJ's treatment took “a pretty hectic and stressful six months,” says Kiran Musunuru, a cardiologist at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia and one of KJ's doctors. “But I think we can make it shorter.”
The trial is also the next step towards answering the question that has been plaguing many of the families of the victims. children with rare diseases since news of KJ's successful treatment broke: when will it be our turn? “There is no one-size-fits-all solution in this area,” says Ryan Maple, executive director of the Global Peroxisomal Disorders Foundation in Tulsa, Oklahoma.
Momentum appears to be building. In addition to the planned clinical trials in Philadelphia, the Center for Pediatric CRISPR Therapies, which opened in July at the University of California, Berkeley, and the University of California, San Francisco, also aims to develop personalized gene editing techniques. And in September, the US government's Health Advanced Research Projects Agency announced two programs to fund research into the development and production of “precision genetic medicine.”
“I'm more optimistic now than I was before,” says Joseph Hasia, a medical geneticist at the Keck School of Medicine at the University of Southern California in Los Angeles.
Therapy for one
Last August, shortly after KJ Muldoon was born, doctors discovered he had a genetic mutation that prevented him from producing the normal form of a crucial liver enzyme called carbamoyl phosphate synthetase 1 (CPS1). CPS1 detoxifies ammonia, a natural waste product created when protein is broken down in the body. Ammonia can damage the brain if not removed from the bloodstream, and many children with CPS1 deficiency do not live to receive the only known cure: liver transplants.
But one of KJ's doctors, Rebecca Ahrens-Niklas of the Children's Hospital of Philadelphia in Pennsylvania, worked with Musunuru to develop a base-editing therapy that could be quickly applied to children with metabolic disorders. KJ will be their first order of business.
At the end of February, KJ underwent database editing therapy designed for him and him alone. CPS1 deficiency occurs in approximately one in a million children. The therapy KJ received was aimed at finding one of the wrong letters in his DNA sequence TsPS1 gene and replace it with another letter that will produce the complete CPS1 protein.
After therapy, KJ's ammonia levels decreased and he was able to reduce his medication. From then on, he worked hard, learned to stand on his own, eat solid food, and tried to take his first steps. “We celebrate every milestone KJ achieves,” says his mother, Nicole Aaron. “He gives off a radiance that really lights up every room he walks into.”
Expanding access
Meanwhile, Musunuru and Ahrens-Niklas were busy developing ways to treat more children. Their research will focus on children with mutations in one of seven genes, including TsPS1that compromise the ability to process ammonia. They plan to use almost exactly the same base editing components that were used for the KJ treatment.
But the researchers will replace one key component of the base editor: a piece of guide RNA that directs the base editor to the DNA letter it replaces. The guide RNA sequence must be tailored to each child's specific mutation.
The US Food and Drug Administration (FDA) typically requires each new formula to undergo a separate clinical trial with safety tests to ensure that the gene editing components are not toxic. But in this case, the FDA said it would accept some data on the safety of KJ's treatment.
With these changes, Musunuru predicts the team will be able to cut the time it takes to develop a therapy from six months to three or four.
Guide for Regulators
The scientists are also publishing much of the written correspondence they had with the FDA to serve as a model for other researchers. The Pennsylvania team will be “a textbook example of the 'rising tide that lifts all boats,'” says Fedor Urnov, who studies genome editing at the University of California, Berkeley's Innovative Genomics Institute (IGI), and helped develop KJ's treatment. “We at IGI will be grateful to ride this wave,” he says.
How far this wave can take everyone is an open question. Musunuru hopes the FDA will consider approving the treatment once 5 to 15 more children have been treated. But researchers will need to find a company that sponsors the app.
“Personalized therapies are definitely the direction we need to go,” says Maple. “This technology could be more than just a game changer. It could be revolutionary.”
This article is reproduced with permission and has been first published October 31, 2025
