On May 15, 2025, medical researchers successfully completed the initial safety phase of a personalized CRISPR-based gene therapy for a six-month-old infant born with carbamoyl phosphate synthetase 1 (CPS1) deficiency, a rare and potentially fatal metabolic condition. The breakthrough treatment was developed and administered at the Children’s Hospital of Philadelphia in partnership with Penn Medicine, using CRISPR base editing to correct a specific CPS1 mutation directly within the child’s liver cells. The therapy, delivered via lipid nanoparticle-based viral vectors, is the first of its kind to be designed for and administered to a single patient.
The development of the therapy was notably rapid. The entire process, from diagnosis to administration, spanned only six months. After diagnosis in late 2024, the infant received an initial low dose at six months of age, followed by a higher dose three weeks later. Medical teams monitored the patient closely, observing steady improvements in clinical and metabolic markers with no serious adverse effects. The infant tolerated the therapy well, signaling encouraging early signs of efficacy.
Following the treatment, the child—referred to publicly as KJ—showed measurable improvements in key metabolic indicators. One of the most significant gains was the ability to increase protein intake in the diet, which had previously been severely restricted due to the body’s inability to process nitrogen properly. In addition, the child required fewer medications designed to reduce toxic ammonia levels in the bloodstream, a critical marker for the disorder. Even after catching a common cold, a typical trigger for dangerous ammonia spikes in CPS1 patients, KJ’s metabolic function remained stable.
CPS1 deficiency is an ultra-rare genetic condition that affects about one in 1.3 million newborns. It typically manifests shortly after birth and can lead to fatal complications if not diagnosed and treated immediately. Survivors often face long-term neurological damage, and the primary treatment option until now has been liver transplantation—an invasive and often delayed procedure in infants who are not yet large enough to undergo surgery safely.
This new gene-editing approach circumvents the need for organ transplantation and represents a milestone in the development of in vivo personalized therapies. Unlike traditional ex vivo gene therapies, which require cells to be edited outside the body and reintroduced later, this therapy edits the genetic code directly inside the patient’s cells. The result is a more targeted and efficient therapeutic approach that could be adapted to other ultra-rare monogenic disorders.
The gene therapy was developed with support from the NIH Common Fund’s Somatic Cell Genome Editing program and included contributions from several partners across academia, clinical research, and industry. These included Acuitas Therapeutics, Integrated DNA Technologies, Aldevron, and Danaher Corporation. The collaboration brought together cutting-edge developments in genome editing, delivery systems, and rapid drug development.
While the early outcomes are highly encouraging, researchers stress that long-term monitoring will be necessary to ensure the safety and durability of the treatment. As with all gene-editing technologies, the potential for off-target effects remains a concern, and scientists will continue to track the child’s response over the coming months and years.
Nonetheless, this trial marks a transformative moment in precision medicine. It not only validates CRISPR base editing as a viable treatment for single-gene disorders but also sets a precedent for the rapid creation of bespoke therapies tailored to individual patients. The scientific and clinical lessons from this case could help unlock a broader pipeline of individualized treatments for patients with rare genetic diseases that are currently untreatable.
With continued investment, collaboration, and regulatory support, experts believe that what was once a singular medical feat could become a new standard for treating the rarest and most challenging conditions. While still experimental, this personalized gene therapy offers hope to families whose children face daunting diagnoses with limited options—and signals a future where tailored cures may become a reality.
