In a historic first for genetic medicine, doctors and scientists at Children’s Hospital of Philadelphia (CHOP) and Penn Medicine have successfully used a customized CRISPR-based gene editing therapy to treat a baby with a rare, life-threatening metabolic condition. The patient, known as KJ, was born with carbamoyl phosphate synthetase 1 (CPS1) deficiency, a disorder that disrupts the body’s ability to process nitrogen, causing toxic ammonia buildup in the blood.
This is the first time in the world that a CRISPR therapy has been specifically tailored and administered to a single patient, marking a revolutionary advancement in personalized medicine.
“Years and years of progress in gene editing and collaboration between researchers and clinicians made this moment possible,” said Dr. Rebecca Ahrens-Nicklas, who led the CHOP team. “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.”
CPS1 deficiency is a urea cycle disorder—a condition where a missing or faulty enzyme prevents the body from eliminating ammonia, a toxic byproduct of protein digestion. In infants, the disease can quickly become fatal or cause severe brain damage.
Traditionally, treatment options have been extremely limited, relying on strict dietary controls and, in some cases, liver transplants. However, liver transplants in newborns pose serious risks and are not always feasible.
Instead, the CHOP-Penn team, including Dr. Kiran Musunuru, opted to create a bespoke gene therapy, specifically designed to correct KJ’s unique genetic mutation. Remarkably, they were able to design, test, and manufacture the treatment in under six months.
KJ received his first infusion in February 2025, followed by two additional doses in March and April. Since then, he has shown steady clinical improvement: tolerating more protein in his diet, needing fewer medications, and recovering from typical childhood illnesses without the dangerous ammonia spikes that previously threatened his life.
“While KJ will need lifelong monitoring, our early results are very encouraging,” said Dr. Ahrens-Nicklas.
What makes this case extraordinary is not just the outcome, but the personalized nature of the therapy. Unlike existing CRISPR treatments developed for more common diseases like sickle cell anemia, this intervention was crafted exclusively for one patient’s rare mutation.
“This is the promise of gene therapy coming to life,” said Dr. Musunuru. “We want to see this approach replicated by other academic teams for many other rare conditions. Every patient deserves the chance at a healthy life.”
The implications are profound. While CRISPR technology has largely focused on large-scale treatments, KJ’s case proves that rapid-response, individualized genetic therapies are not only possible—but effective. It offers a new model for tackling ultra-rare diseases, many of which currently have no treatments at all.
This success story could mark the beginning of a new era in medicine, where rare is no longer untreatable, and precision therapies can be crafted in real time to save lives.
By Impact Lab
