KJ: The First of Many

In early 2025, physicians at the Children's Hospital of Philadelphia and Penn Medicine made medical history by treating the world's first patient with a personalized CRISPR gene editing therapy matched to his unique genetic profile. This personalized intervention may mark a turning point in how rare genetic diseases might someday be treated.

  The young patient, known as KJ, was born with a rare metabolic disorder called severe carbamoyl phosphate synthetase 1, or CPS1, a genetic condition that inhibits the body's metabolization process. CPS1 leads to a toxic ammonia buildup that can damage vital organs, especially the brain and liver. Traditionally, liver transplant is the only fundamental treatment option for this disease, but many infants are too fragile to endure such a major surgery.

  While KJ spent the first few months of his life in the hospital on a restricted diet, doctors raced to develop a treatment tailored to his distinctive genome. The medical team, led by Dr. Rebecca Ahrens-Nicklas and Dr. Kiran Musunuru, manufactured a gene editing therapy that used CRISPR-based “base editing” delivered through lipid nanoparticles directly to KJ’s liver cells. This gene therapy, unlike the traditional ones aimed at broader populations, served KJ’s exact disease.

Newborn KJ at Children’s Hospital of Philadelphia. Photo via Children’s Hospital Philadelphia

At barely seven months old, KJ got his first infusion of the drug. He had two more doses over the next several months without any serious side effects reported. Early results suggest that KJ is more tolerant to dietary protein and less reliant on medication since the drug was administered. 

This type of gene editing is revolutionary, because it denotes a major shift in the approach toward genetic medicine. Many diseases result from different mutations, making it difficult to develop one-size-fits-all therapies. KJ's case highlights that therapies tailored for individuals may soon become a reality. Researchers also say that although the results are promising at this early stage, monitoring would be required. They express hope that this method can be replicated and adapted for countless other rare genetic disorders, giving many patients who currently lack effective treatments a real chance at a healthy life.