KJ Muldoon, the first patient treated with a personalised CRISPR therapy, for CPS1 deficiency

On 15 May 2025, Children’s Hospital of Philadelphia (CHOP) and Penn Medicine announced that a baby, KJ Muldoon, had become the first patient treated with a CRISPR gene-editing therapy made specifically for his mutation. The case was published the same day in The New England Journal of Medicine and presented at the American Society of Gene & Cell Therapy annual meeting.

What CPS1 deficiency is

Severe carbamoyl-phosphate synthetase 1 (CPS1) deficiency is a rare urea cycle disorder. The liver cannot turn ammonia into urea, so ammonia builds up to toxic levels that can damage the brain and liver. The authors estimate about 50% mortality in early infancy. The standard treatment is a liver transplant, which requires the child to be stable enough and large enough for surgery.

What the team did

KJ was diagnosed within days of birth and spent his first months in hospital on a very restricted diet. A team led by Dr Rebecca Ahrens-Nicklas (CHOP) and Dr Kiran Musunuru (Penn) designed and manufactured, in about six months, a base editor, a form of CRISPR editing that can correct a specific genetic variant. The therapy is carried to the liver in lipid nanoparticles. KJ received his first infusion in February 2025, at about seven months of age; the hospital reported three doses by April 2025.

In the seven weeks after the first infusion, KJ could take more protein in his diet, and his nitrogen-scavenger medicine was cut to half the starting dose, despite viral illnesses. No serious adverse events were reported. He went home in June 2025, and in December 2025 the hospital reported that he had taken his first steps.

What it means for patients now

This is a single patient followed for a short time. The authors stress that longer follow-up is needed to judge safety and effectiveness, and KJ will be monitored for life. In August 2026, CHOP started a phase 1/2 clinical trial (NCT07667387) at a single site in Philadelphia for children with severe, infantile-onset urea cycle disorders caused by variants that this method can correct. The therapy remains experimental. Families of children with rare metabolic diseases can ask their genetics specialist whether such a trial might be relevant.