CHOP and Penn treat an infant with a personalized CRISPR base-editing therapy for CPS1 deficiency

The Lazaretto keeps its watch on the water-world’s medicine.

On May 15, 2025, researchers at Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania reported the first treatment of a patient with a customized, patient-specific CRISPR base-editing therapy. The infant, known publicly as KJ, was born with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, a rare urea cycle disorder in which toxic ammonia builds up in the blood. The condition carries a high risk of death or neurological injury in infancy.

The team designed a base editor paired with a bespoke guide sequence and delivered it to the liver using lipid nanoparticles. KJ received escalating doses between roughly six and eight months of age. The therapy was designed and manufactured in about six months. After treatment, the child tolerated more dietary protein, required less medication, and reached developmental milestones.

The case was presented at the American Society of Gene and Cell Therapy annual meeting and published in the New England Journal of Medicine. “While KJ is just one patient, we hope he is the first of many to benefit from a methodology that can be scaled to fit an individual patient’s needs,” said Dr. Rebecca Ahrens-Nicklas, who directs CHOP’s gene therapy program for inherited metabolic disorders. Dr. Kiran Musunuru of Penn said he hoped other investigators would replicate the method for many rare diseases.