In a historic first for precision medicine, a research team supported by the National Institutes of Health (NIH) has successfully delivered a personalized CRISPR-based gene-editing therapy to treat an infant diagnosed with a rare and life-threatening genetic condition—carbamoyl phosphate synthetase 1 (CPS1) deficiency. The groundbreaking treatment marks the first known use of patient-specific CRISPR gene editing to correct a genetic mutation inside the human body and could pave the way for rapid, customized treatments for other rare diseases.
The infant was diagnosed with CPS1 deficiency shortly after birth. The condition, which affects the liver’s ability to break down nitrogen waste, results in toxic ammonia buildup in the body. Without intervention, the disorder can quickly lead to brain swelling, coma, or death. Traditional management includes strict dietary restrictions and, eventually, liver transplantation—but the critical period before transplant poses extreme risks, especially during illness or injury.
To address this urgent medical challenge, researchers at the Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania’s Perelman School of Medicine developed a tailored CRISPR-based therapy that precisely corrected the infant’s unique mutation. The treatment targeted non-reproductive liver cells, ensuring changes affected only the patient and not future generations.
“We knew the delivery platform allowed for repeated dosing, so we began with a very low, safe dose,” explained Dr. Rebecca Ahrens-Nicklas, pediatrician at CHOP. The infant received the first dose at six months of age, followed by a higher dose. Improvements were evident shortly after: the child tolerated more dietary protein, and medications required to control ammonia levels were gradually reduced.
The most compelling sign of progress came during a common childhood illness. “We were very concerned when the baby got sick, but the baby just shrugged the illness off,” said Dr. Kiran Musunuru, lead author and professor of cardiovascular medicine and genetics at Penn. This resilience, unheard of in untreated CPS1 patients, strongly suggested the therapy had taken effect.
The work was announced on May 15, 2025, at the American Society of Gene & Cell Therapy Annual Meeting and published the same day in The New England Journal of Medicine. The study—entitled Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease—describes the unprecedented effort to take a treatment from diagnosis to delivery in just six months.
This success builds on NIH’s broader efforts to accelerate gene-editing research. The project was supported by multiple NIH grants, including from the NIH Common Fund’s Somatic Cell Genome Editing program and the National Heart, Lung, and Blood Institute. Additional support came from CHOP’s Gene Therapy for Inherited Metabolic Disorders Frontier Program, and industry partners including Acuitas Therapeutics and Integrated DNA Technologies.
“This is a pivotal moment,” said Dr. Joni L. Rutter, Director of NIH’s National Center for Advancing Translational Sciences. “It shows that with reusable gene-editing platforms and rapid customization, we can bring life-saving therapies to patients when time matters most—early, fast, and personalized.”
While long-term follow-up is still underway, researchers remain cautiously optimistic. The personalized therapy not only offers hope for this child, but also lays the foundation for adapting the approach to hundreds of other rare genetic diseases, many of which currently have no treatment options.
About NIH: The National Institutes of Health (NIH) is the U.S. government’s primary medical research agency. Comprising 27 Institutes and Centers, NIH supports basic, clinical, and translational research aimed at understanding and treating common and rare diseases. For more, visit www.nih.gov.
Reference:
Musunuru et al., Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease, New England Journal of Medicine, May 15, 2025.
