On May 15, 2025, a team at Children’s Hospital of Philadelphia (CHOP) and Penn Medicine announced that a child diagnosed with a rare genetic disorder has been successfully treated with a customized CRISPR gene editing therapy in a historic worlds first.

The infant, KJ, was born with a rare metabolic disease known as severe carbamoyl phosphate synthetase 1 (CPS1) deficiency. After spending the first several months of his life in the hospital, on a very restrictive diet, KJ received the first dose of his bespoke therapy in February 2025 between six and seven months of age. The treatment was administered safely, and he is now growing well and thriving.

The case is detailed today in a study published by The New England Journal of Medicine and was presented at the American Society of Gene & Cell Therapy Annual Meeting in New Orleans. This landmark finding could provide a pathway for gene editing technology to be successfully adapted to treat individuals with rare diseases for whom no medical treatments are available.

CRISPR (clustered regularly interspaced short palindromic repeats)-based gene editing can precisely correct disease-causing variants in the human genome. Gene editing tools are incredibly complex and nuanced, and up to this point, researchers have built them to target more common diseases that affect tens or hundreds of thousands of patients, such as the two diseases for which there currently are U.S. Food and Drug Administration-approved therapies, sickle cell disease and beta thalassemia.

As of April 2025, KJ had received three doses of the therapy with no serious side effects. In the short time since treatment, he has tolerated increased dietary protein and needed less nitrogen scavenger medication. He also has been able to recover from certain typical childhood illnesses like rhinovirus without ammonia building up in his body. Longer follow-up is needed to fully evaluate the benefits of the therapy.

Typically, patients with CPS1 deficiency, like KJ, are treated with a liver transplant. However, for patients to receive a liver transplant, they need to be medically stable and old enough to handle such a major procedure.

During that time, episodes of increased ammonia can put patients at risk for ongoing, lifelong neurologic damage or even prove fatal. Because of these threats to lifelong health, the researchers knew that finding new ways to treat patients who are too young and small to receive liver transplants would be lifechanging for families whose children faced this disorder.