In May 2025, doctors in Philadelphia successfully performed the world’s first in vivo CRISPR gene-editing treatment on an infant diagnosed with a rare and life-threatening genetic disorder — carbamoyl phosphate synthetase 1 deficiency (CPS1). This breakthrough may pave the way for treating numerous other rare diseases using personalized genetic medicine.
The patient, nine-month-old KJ Muldoon, suffered from a severe form of CPS1 deficiency, which prevents the body from processing ammonia, leading to toxic levels in the blood. Without intervention, the condition is often fatal in infancy. Previously, treatment options were limited to strict dietary control and eventual liver transplantation.
Researchers from the Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania developed a custom CRISPR-Cas9 therapy targeted at correcting the specific mutation in KJ’s liver cells. The treatment involved lipid nanoparticles delivering RNA and a guide sequence directly to the liver, editing the DNA inside the body without removing any cells.
KJ received his first dose in February 2025 at six months old. Within days, his metabolic response improved, showing better protein tolerance, reduced medication dependency, and healthy weight gain. He has since received two more, higher-dose infusions and continues under medical observation.
This case marks the first successful application of personalized CRISPR gene therapy for a rare disorder in a human. Experts say it represents a milestone in precision medicine, opening possibilities for patients with other untreatable genetic conditions.
While scientists caution that more research is needed to assess long-term safety and efficacy, the case is already being hailed as a scientific milestone.
