In a medical breakthrough that could redefine treatment for rare genetic diseases, a six-month-old infant with a previously incurable liver disorder has become the first person to receive a personalized CRISPR-based gene therapy. The treatment, developed in just six months, was led by researchers at the Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania, with funding and support from the U.S. National Institutes of Health (NIH).

The child was born with carbamoyl phosphate synthetase 1 (CPS1) deficiency, a rare condition that causes toxic ammonia to accumulate in the body, leading to severe brain and liver damage. Existing treatments typically involve restrictive diets and eventual liver transplants, with considerable risks in the early months of life. This pioneering case shows how gene editing platforms can now be tailored rapidly and safely for individuals with life-threatening diseases.

The customized therapy was developed using CRISPR, a gene-editing technology that allows scientists to make precise changes to DNA in living cells. In this case, the researchers targeted the infant’s liver cells to correct the CPS1 gene mutation—without affecting reproductive cells, ensuring the changes would not be passed on genetically.

“This is a remarkable moment,” said Joni L. Rutter, Ph.D., director of NIH’s National Center for Advancing Translational Sciences (NCATS). “As a platform, gene editing — built on reusable components and rapid customization — promises a new era of precision medicine for hundreds of rare diseases, bringing life-changing therapies to patients when timing matters most: Early, fast, and tailored to the individual.”

The child first received a low dose of the therapy at six months old, followed by a higher dose. According to the team, signs of improvement were seen almost immediately. The infant tolerated more protein in their diet, needed less medication to manage ammonia levels, and crucially, responded well to common childhood illnesses—an indicator of treatment resilience.

“We knew the method used to deliver the gene-editing machinery to the baby’s liver cells allowed us to give the treatment repeatedly. That meant we could start with a low dose that we were sure was safe,” said Dr. Rebecca Ahrens-Nicklas, pediatrician and geneticist at CHOP.

The most telling moment came when the baby contracted a cold and later a gastrointestinal illness—conditions that normally pose a grave threat to children with CPS1 deficiency. “We were very concerned when the baby got sick, but the baby just shrugged the illness off,” said first author and Penn geneticist Dr. Kiran Musunuru. “It was a clear sign the therapy was working.”

The study was presented at the American Society of Gene & Cell Therapy Meeting on May 15 and published in The New England Journal of Medicine.

Funding for the project came from several NIH programs including the Somatic Cell Genome Editing program and the National Heart, Lung, and Blood Institute, with contributions from CHOP’s Gene Therapy Frontier Program and biotech partners including Acuitas Therapeutics and Integrated DNA Technologies.

While researchers remain cautious, the success of this patient-specific treatment could revolutionize how rare diseases are managed, ushering in a future of hyper-personalized and fast-tracked therapies.