The historic utilization of gene editing CRISPR technology to treat a baby boy with a rare, incurable condition known as carbamoyl phosphate synthetase 1 (CPS1) deficiency represents a turning point in medicine, opening the possibility of personalized treatments in all parts of the body.
A research team from the Children’s Hospital of Philadelphia (CHOP), the Perelman School of Medicine at the University of Pennsylvania, and supported by the National Institutes of Health (NIH) developed the therapy using the gene-editing platform CRISPR, which is an advanced gene-editing technology that enables precise changes to DNA inside living cells.
The process took only 6 months and marks the first time this treatment has been successfully deployed to treat a human patient.
The research team corrected a specific gene mutation in the baby’s liver cells that led to CPS1 deficiency, which is characterized by an inability to fully break down byproducts from protein metabolism in the liver, causing ammonia to build up to toxic levels in the body. It can cause severe damage to the brain and liver. Treatment includes a low protein diet until the child is old enough for a liver transplant. However, in this waiting period there is a risk of rapid organ failure due to stressors such as infection, trauma, or dehydration. High levels of ammonia can cause coma, brain swelling, and may be fatal or cause permanent brain damage.
The child initially received a very low dose of the therapy at 6 months of age in February 2025, then a higher dose later. The research team saw signs that the therapy was effective almost from the start.
“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,” CHOP pediatrician Rebecca Ahrens-Nicklas, MD, PhD, explained in a statement about the treatment.1
The 6-month-old began taking in more protein in the diet, and the care team could reduce the medicine needed to keep ammonia levels low in the body. Another telling sign of the child’s improvement to date came after the child caught a cold, and later, had to deal with a gastrointestinal illness. Normally, such infections for a child in this condition could be extremely dangerous, especially with the possibility of ammonia reaching dangerous levels in the brain.
“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,” Joni L. Rutter, PhD, Director of NIH’s National Center for Advancing Translational Sciences, said in a prepared statement about the treatment.
The scientists announced their work at the American Society of Gene and Cell Therapy Meeting on May 15, 2025, and described the study in the New England Journal of Medicine.2
Funding for this project was provided by the NIH Common Fund Somatic Cell Genome Editing program grants, U01TR005355, U19NS132301, U19NS132303, DP2CA281401, and National Heart, Lung, and Blood Institute grants R35HL145203 and P01HL142494. In-kind contributions for the study were made by Acuitas Therapeutics, Integrated DNA Technologies, Aldevron, and Danaher Corporation. Additional funding was provided by the CHOP Research Institute’s Gene Therapy for Inherited Metabolic Disorders Frontier Program.
References
- National Institutes of Health. Infant with rare, incurable disease is first to successfully receive personalized gene therapy treatment. May 15, 2025. Accessed May 15, 2025. www.nih.gov/news-events/news-releases/infant-rare-incurable-disease-first-successfully-receive-personalized-gene-therapy-treatment
- Musunuru K, Grandinette SA, Wang X, et al. Patient-specific in vivo gene editing to treat a rare genetic disease. N Engl J Med. 2025;392:2235-2243.
