In late 2024, a remarkable medical breakthrough unfolded as a team of researchers and physicians collaborated across great distances to save the life of a baby boy named KJ Muldoon. Their success marked the first time a personalized gene-editing therapy had been created and administered to a single patient in an unprecedentedly short span of six months. This pioneering effort not only saved KJ’s life but also set the stage for a new era in the treatment of rare genetic diseases, one in which bespoke gene-editing therapies could potentially help thousands of other children worldwide.
The therapy that saved KJ utilized an advanced form of gene editing known as base editing, a refined offshoot of the widely known CRISPR–Cas9 technique. Unlike traditional CRISPR methods that cut DNA strands, base editing enables scientists to make precise, single-letter changes in the DNA sequence, effectively correcting mutations at their source without introducing breaks in the DNA. This precision and safety profile make base editing a promising tool for treating genetic disorders caused by single-letter mutations.
KJ’s condition was caused by a mutation in the gene responsible for producing carbamoyl phosphate synthetase 1 (CPS1), a critical enzyme in the liver that detoxifies ammonia, a harmful byproduct generated when the body metabolizes protein. Without functional CPS1, ammonia accumulates in the bloodstream, leading to severe brain damage and, in many cases, early death. The only existing cure for CPS1 deficiency was a liver transplant, a complex and risky procedure with limited availability. Faced with the urgency of KJ’s condition, his medical team, led by Dr. Rebecca Ahrens-Nicklas at the Children’s Hospital of Philadelphia and cardiologist Dr. Kiran Musunuru at the University of Pennsylvania, turned to base editing as a last resort.
In February 2025, KJ received a gene-editing therapy tailored exclusively for him. The treatment was designed to locate the specific faulty DNA letter in his CPS1 gene and replace it with the correct one, restoring the production of the enzyme. The results were encouraging: KJ’s ammonia levels dropped, he was able to reduce his medications, and he began reaching developmental milestones like standing and eating solid foods. His mother, Nicole Aaron, described his progress with heartfelt joy, noting how his vibrant spirit brightened every room he entered.
The success of KJ’s personalized therapy has galvanized the medical and scientific community to expand this approach. Musunuru and Ahrens-Nicklas are now preparing to launch a clinical trial that aims to treat at least five more children with similar metabolic disorders caused by mutations in one of seven genes related to ammonia processing, including CPS1. The upcoming trial, set to begin in 2026, will use largely the same base-editing components developed for KJ’s treatment. The key difference will be in customizing the RNA guide sequence, which directs the base editor to the precise DNA letter that needs correction in each patient’s genome.
One of the major hurdles in developing personalized gene therapies has been the regulatory process. Typically, the US Food and Drug Administration (FDA) requires each new formulation of a gene-editing therapy to undergo separate clinical trials and safety evaluations, a process that can take years. However, in a significant and encouraging development, the FDA has agreed to accept some of the safety data from KJ’s treatment as part of the approval process for the new trial. This regulatory flexibility could drastically reduce the time needed to prepare personalized therapies, potentially cutting development periods from six months to just three or four.
To help other researchers navigate this complex regulatory landscape, Musunuru’s team has published much of their correspondence with the FDA. Their transparency aims to serve as a model, encouraging a “rising tide that lifts all boats,” as described by Fyodor Urnov of the Innovative Genomics Institute at the University of California, Berkeley, who was instrumental in creating KJ’s treatment.
The broader scientific community is watching these developments with optimism. The Center for Pediatric CRISPR Cures, established in mid-2025 through a collaboration between the University of California, Berkeley and the University of California, San Francisco, is also dedicated to developing personalized gene-editing therapies for children with rare diseases. Further support has come from the US government’s Advanced Research Projects Agency for Health, which recently launched two funding programs focused on precision genetic medicine research and manufacturing.
Despite this momentum, challenges remain. Securing commercial partners to sponsor regulatory