CRISPR (clustered regularly interspaced short palindromic repeats)-based gene editing can correct disease-causing variants in the human genome. However, many diseases do not benefit from a “one-size-fits-all” approach because they can have various disease-causing variants.
Gene editing tools are complex, and researchers have primarily focused on targeting diseases such as sickle cell disease and beta-thalassemia, for which the Food and Drug Administration has already approved therapies.
In 2023, researchers and clinicians at the Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania began collaborating to explore the possibility of creating customized gene editing therapies for individual patients.
Their groundbreaking research highlights a successful personalized CRISPR gene editing therapy developed to treat a baby named KJ, who was diagnosed with carbamoyl phosphate synthetase 1 (CPS1) deficiency, a rare genetic disorder.
Typically, patients with CPS1 deficiency, like KJ, are treated with a liver transplant.
However, to be eligible for a transplant, they must be medically stable and old enough to undergo such a significant procedure. During the waiting period, episodes of increased ammonia can pose risks of lifelong neurological damage or even death.
Recognizing these risks, the researchers understood that finding new treatment options for very young or small patients who were not candidates for liver transplants could be life-changing for families facing this disorder.
Days after his birth, KJ was transferred to the Children’s Hospital of Philadelphia, where doctors were actively researching new cell and gene therapies.
After spending the first few months of his life in the hospital on a restrictive diet, KJ received his first dose of the custom treatment in February 2025, when he was between six and seven months old.
The treatment was administered safely, and KJ has since grown and thrived.
The research team targeted KJ’s specific CPS1 variant, which was identified shortly after his birth.
Within six months, they designed and manufactured a base editing therapy delivered via lipid nanoparticles to his liver to correct the faulty enzyme.
KJ received his first infusion of this experimental therapy in late February 2025, followed by additional doses in March and April 2025.
This landmark finding could pave the way for gene editing technology to treat individuals with rare diseases.
Last week, the American Society of Gene and Cell Therapy held its 28th Annual Meeting for professionals in the field. CHOP and the University of Pennsylvania researchers presented a significant study published in the New England Journal of Medicine during the conference.
This study details the rigorously yet swiftly developed customized CRISPR gene editing therapy for baby KJ.
As of April 2025, KJ had received three therapy doses with no serious side effects.
Remarkably, since starting treatment, he has tolerated increased dietary protein and required less nitrogen-scavenging medication.
He has also recovered from common childhood illnesses, such as rhinovirus, without experiencing ammonia buildup in his body.
However, longer follow-up is necessary to evaluate the therapy’s benefits fully.
This study received support from the National Institutes of Health Somatic Cell Genome Editing Program and additional NIH grants.
Acuitas Therapeutics, Integrated DNA Technologies, Aldevron, and the Danaher Corporation contributed, while the CHOP Research Institute’s Gene Therapy for Inherited Metabolic Disorders Frontier Program provided further funding.
CHOP & @PennMedicine have delivered the first-ever personalized gene editing therapy for a patient with CPS1 deficiency, marking a major milestone in the application of CRISPR-based treatments.
Learn more about KJ & the future of personalized medicine: https://t.co/A9DTcNmxrR. pic.twitter.com/2LzGiRxGqN
— Children's Hospital (@ChildrensPhila) May 15, 2025
The American Society of Gene and Cell Therapy's 28th Annual Meeting starts today. Discover the latest scientific research and new technologies in gene and cell therapy #ASGCT2025 (May 13 – 17, 2025 in New Orleans) #genetherapy https://t.co/TXroAZnDCP pic.twitter.com/KVSi6lULpM
— The Cure Sickle Cell Initiative (CureSCi) (@thecuresci) May 13, 2025
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