Researchers at Children’s Hospital of Philadelphia and Penn Medicine have achieved a medical first by treating baby K.J. Muldoon—born with a rare, often fatal carbamoyl phosphate synthetase 1 (CPS1) deficiency—with a personalized CRISPR-based gene‑editing therapy.
Diagnosed shortly after birth due to dangerously high ammonia levels, K.J. faced a grim outlook that typically demands a liver transplant and carries high neurological risks.
Within just six months, a multidisciplinary team led by Dr. Kiran Musunuru and Dr. Rebecca Ahrens‑Nicklas sequenced K.J.’s genome, identified his unique mutations, and designed “kayjayguran,” a bespoke base‑editing CRISPR therapy delivered via lipid nanoparticles directly to his liver.
The FDA granted rapid regulatory clearance under a “forward‑leaning” review process, allowing the first low‑dose infusion when K.J. was nearly seven months old, followed by two additional doses as he tolerated the treatment safely.
Early results are encouraging: K.J. is gaining weight, meeting developmental milestones, and requires less ammonia‑scavenging medication. He can even enjoy foods like avocado—an important protein source previously too risky for him.
Unlike CRISPR therapies that edit stem cells ex vivo, this in‑body approach represents a leap forward in precision medicine, directly correcting the defective gene in situ.
“This amazing constellation of scientists … wove them together and administered treatments to a child who was destined for devastating disability,” said Fyodor Urnov of the Innovative Genomics Institute, highlighting the collaborative spirit and decades of foundational research underpinning the effort.
Ethicists caution that long‑term follow‑up is essential to monitor potential off‑target effects and to understand how durable the benefit will be. There are also open questions about scalability and cost, since bespoke therapies today rely on substantial in‑kind contributions from industry partners.
Still, this landmark case paves the way for an “N‑of‑1” model of ultra‑rare disease treatment, where an individual’s unique mutation can be targeted rapidly and precisely. If further trials validate safety and efficacy, we may soon see a new era where one‑off genetic drugs move from concept to clinic in mere months.
Learn how personalized gene editing saved baby KJ’s life. Watch the inspiring video about this breakthrough.
For the full story on how K.J.’s personalized CRISPR therapy is rewriting the rules of genetic medicine, check out the Wall Street Journal article and accompanying reports.
