In a historic medical breakthrough, a child diagnosed with a rare genetic disorder was successfully treated with a personalized CRISPR gene-editing therapy by a group from the Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania’s Perelman School of Medicine (Penn Medicine). The infant, named KJ Muldoon, was born with a rare metabolic disease known as Severe Carbamoyl Phosphate Synthetase 1 Deficiency (CPS1). After spending the first months of life in the hospital on a very restricted diet, KJ received the first dose of his personalized therapy in February 2025, at around six to seven months old. The treatment was administered safely, and he is now developing well. KJ was diagnosed with the rare metabolic disorder just days after birth and transferred to CHOP, where doctors were actively researching new cellular and gene therapies.
This case is presented today in a study published in The New England Journal of Medicine and was showcased at the Annual Meeting of the American Society of Gene & Cell Therapy in New Orleans. This milestone could pave the way for the successful adaptation of gene-editing technology to treat individuals with rare diseases for which no medical therapies currently exist.
CRISPR-based gene editing (clustered regularly interspaced short palindromic repeats) can precisely correct disease-causing variants in the human genome. Gene-editing tools are highly complex and have so far been designed for more common diseases such as sickle cell anemia and beta-thalassemia, for which FDA-approved treatments exist. However, few diseases benefit from a “one-size-fits-all” approach, as there are too many disease-causing variants. Thus, many patients with rare genetic diseases—affecting millions worldwide—have been left behind. Researchers at CHOP and Penn began studying in 2023 the possibility of creating personalized gene-editing therapies for individual patients, building on years of research into rare metabolic disorders. They focused on urea cycle disorders, where the lack of an enzyme in the liver leads to toxic ammonia buildup, causing brain and liver damage. After years of preclinical research, the team designed and produced a base-editing therapy delivered via lipid nanoparticles to the liver to correct KJ’s defective enzyme. In February 2025, KJ received the first infusion of this experimental therapy, followed by doses in March and April 2025. By April, he had received three doses without serious side effects, showed improved feeding, reduced need for medication, and recovered from childhood infections without ammonia accumulation.
Long-term monitoring remains essential to fully assess the treatment’s benefits, but early results are encouraging. Researchers hope this method will become a model for treating many rare diseases, giving many patients the chance for a healthy life.