Global success: Baby thrives after receiving innovative personalized CRISPR gene therapy for rare disease.

CRISPR has been used to develop a gene therapy option for a child born in Pennsylvania affected by a rare metabolic disorder.

The newborn, KJ, could not convert ammonia to urea, putting him at serious risk of brain or liver damage and needed to be maintained on medication and an extremely restrictive diet to prevent protein metabolism.

Doctors at Children’s Hospital of Philadelphia (CHOP) believed they could use CRISPR to develop a treatment that would correct a defective gene in KJ’s genome, essentially curing him.

KJ’s parents, Nicole and Kyle Muldoon, decided to entrust their son’s well-being to two pioneering genetic therapists, Dr. Rebecca Ahrens-Nicklas and Dr. Kiran Musunuru, who designed a personalized treatment that has successfully corrected the genetic defect.

“Years and years of progress in gene editing and collaboration between researchers and clinicians made this moment possible, and although KJ is just one patient, we hope he will be the first of many who will benefit from a methodology that can be tailored to the needs of each individual patient,” said Rebecca Ahrens-Nicklas, MD, PhD, director of the Frontier Gene Therapy for Inherited Metabolic Disorders (GTIMD) Program at Children’s Hospital of Philadelphia.

She, along with Dr. Musunuru, are members of the NIH-funded Somatic Cell Genome Editing Consortium, and have spent years developing the science of using CRISPR to create individual treatment doses for the rarest diseases.

So far, the only CRISPR therapies approved and standardized by the FDA target two diseases that affect tens of thousands of patients. CRISPR is an incredibly complex and expensive tool to wield, leaving its magic out of reach for millions of children and adults around the world who collectively suffer from extremely rare genetic disorders.

One such disorder is called severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, which prevents the proper conversion of ammonia to urea to be excreted through urine. Ammonia is created in the body through protein metabolism. CPS1 is created in the liver to convert it into urea and thus avoid the toxic effects of the former.

KJ’s body can’t do it, so excess protein metabolism creates a buildup of ammonia in his liver that could be fatal. Nitrogen uptake medications and a protein-deficient diet can sustain the patient until a liver transplant can be found, but at only months old, KJ’s body is not able to withstand the procedure.

A CHOP news release reports that Ahrens-Nicklas and Musunuru zeroed in on KJ’s specific CPS1 variant after years of work with similar disease-causing variants. Within six months, his team designed and manufactured a base-editing therapy delivered via lipid nanoparticles to the liver to correct the defective KJ enzyme.

In late February 2025, KJ received his first infusion of this experimental therapy, and has since received follow-up doses in March and April 2025, the statement details. In the newly published New England Journal of Medicine article, the researchers, along with their academic and industrial collaborators, describe the personalized CRISPR gene-editing therapy that was rigorously but rapidly developed to be administered to KJ.

KJ has received 3 doses and has had no side effects. He has been able to stop the medication and reintroduce some protein into his diet, although he will need careful monitoring for the rest of his life.

“We thought it was our responsibility to help our son, so when the doctors came to us with their idea, we trusted them in hopes that it could help not only KJ but other families in our situation,” his mother, Nicole, told CHOP.