First Personalized CRISPR Therapy – A Child's Life Saved in Six Months

A Race Against Time

When KJ was just days old, doctors diagnosed him with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency—a rare metabolic disorder affecting approximately one in 100,000 newborns. The diagnosis set in motion a medical race unlike any before.

CPS1 deficiency disrupts the urea cycle, the biochemical pathway that converts nitrogen waste from protein metabolism into urea for excretion. Without functioning CPS1 enzyme, toxic ammonia accumulates in the blood, particularly after eating protein. The consequences are severe: brain damage, developmental delays, coma, and frequently death.

Standard treatment involves severely restricting dietary protein and administering nitrogen-scavenging medications—drugs that help the body eliminate nitrogen through alternative pathways. But these measures are imperfect. Patients remain vulnerable to ammonia crises, particularly during illness or metabolic stress. Many require liver transplantation, the only definitive treatment, which carries its own significant risks.

KJ’s family and medical team faced this stark reality. But they also had an opportunity that patients with this condition had never had before: the possibility of personalized gene therapy.

Building a Custom Treatment

What made KJ’s case historic wasn’t just that he received gene therapy. It was how quickly and specifically that therapy was created.

Researchers at Children’s Hospital of Philadelphia (CHOP) and Penn Medicine had been developing gene-editing approaches for metabolic diseases for years. When KJ was diagnosed, they already had a foundation of preclinical work with similar genetic variants. But turning that foundation into a treatment for one specific patient required extraordinary coordination.

The team, led by Dr. Rebecca Ahrens-Nicklas at CHOP and Dr. Kiran Musunuru at Penn Medicine, identified KJ’s specific genetic mutation immediately after diagnosis. They then designed a base-editing therapy—a precise form of CRISPR gene editing that changes individual DNA letters without cutting the double helix—customized to correct his particular variant.

Manufacturing the therapy, formulating it in lipid nanoparticles capable of delivering it to liver cells, and completing the necessary safety testing took approximately six months. By historical standards of drug development, this was astonishingly fast.

“Years and years of progress in gene editing and collaboration between researchers and clinicians made this moment possible,” Dr. Ahrens-Nicklas reflected.

The Treatment

In February 2025, at roughly six months old, KJ received his first infusion of the personalized therapy. The treatment was delivered intravenously, with the lipid nanoparticles carrying the base-editing instructions specifically targeting his liver—the organ responsible for urea cycle function.

KJ received two additional doses in March and April 2025. Throughout the treatment, he experienced no serious adverse effects.

The results, published in the New England Journal of Medicine in May 2025, demonstrated meaningful clinical improvement. KJ was able to tolerate increased protein in his diet—crucial for growth and development. His need for nitrogen-scavenging medication decreased. His ammonia levels remained more stable.

Perhaps most significantly, when KJ contracted a rhinovirus—a common cold that would typically trigger dangerous ammonia accumulation in patients with his condition—his ammonia levels remained stable. He recovered without crisis.

“We thought it was our responsibility to help our child,” KJ’s mother, Nicole Muldoon, said, “so when the doctors came to us with their idea, we put our trust in them.”

The Significance of “N-of-1”

Medical researchers use the term “N-of-1” to describe treatments designed for a single patient. Such approaches have long been theoretically possible but practically challenging. The time, cost, and regulatory complexity of developing a treatment for one person seemed prohibitive.

KJ’s case demonstrates that N-of-1 gene therapy is now feasible—at least for conditions where the underlying biology is well understood and the therapeutic target is clear.

The implications extend far beyond CPS1 deficiency. There are approximately 7,000 known rare genetic diseases, most affecting only a handful of patients. Collectively, rare diseases affect an estimated 25 to 30 million Americans. For many of these conditions, no approved treatments exist—the patient populations are too small to support traditional drug development economics.

Personalized gene therapy could change this equation. If treatments can be designed and manufactured quickly enough, and if regulatory pathways can accommodate individual patients, diseases that are currently untreatable could become addressable.

Challenges Ahead

Despite the historic achievement, significant challenges remain before personalized gene therapy becomes widely available.

Cost is perhaps the most obvious barrier. Developing a treatment for one patient, including all the research, manufacturing, and testing required, is expensive. How such treatments would be paid for—by insurance, by research institutions, by government programs—remains unclear.

Regulatory frameworks are still evolving. The FDA and other regulatory agencies have shown willingness to work with researchers on compassionate use and investigational treatments, but systematic pathways for approving personalized therapies don’t fully exist.

Manufacturing capacity is limited. Creating custom gene therapies requires specialized facilities and expertise that aren’t widely available. Scaling this approach to serve more patients would require substantial infrastructure investment.

And while KJ’s short-term results are encouraging, long-term outcomes remain unknown. Gene editing is permanent, and monitoring will continue for years to understand the durability of benefit and to watch for any delayed adverse effects.

A Transformation in Medicine

Despite these challenges, researchers involved in KJ’s care see this case as a harbinger of fundamental change in how medicine approaches genetic disease.

“The promise of gene therapy that we’ve heard about for decades is coming to fruition,” Dr. Musunuru observed, “and it’s going to utterly transform the way we approach medicine.”

That transformation won’t happen overnight. But for the first time, the pieces are falling into place: gene-editing technologies precise enough to correct individual mutations, delivery systems capable of reaching target tissues, manufacturing processes fast enough to respond to individual patients, and institutional commitment to pushing the boundaries of what’s possible.

For families like KJ’s, who face diagnoses that once offered little hope, these advances represent something profound. Not just better treatment options, but the possibility that their child’s specific genetic inheritance doesn’t have to determine their future.

KJ continues to grow and thrive. His story, documented in one of medicine’s most prestigious journals, will likely be followed by others. The era of truly personalized genetic medicine has begun.

Sources

1. Ahrens-Nicklas R, Musunuru K, et al. “Patient-Specific In Vivo Gene Editing to Treat a Rare Genetic Disease.” New England Journal of Medicine. May 2025. DOI: 10.1056/NEJMoa2504747

2. Children’s Hospital of Philadelphia. “World’s First Patient Treated with Personalized CRISPR Gene Editing Therapy at Children’s Hospital of Philadelphia.” May 2025. https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital