A Historic Breakthrough in Genetic Science
A team of specialists at the Children’s Hospital of Philadelphia (CHOP) and Penn Medicine have achieved a groundbreaking success by treating an infant diagnosed with a rare genetic condition through a specially tailored CRISPR-based gene editing therapy. Baby KJ was born with the genetic anomaly known as carbamoyl phosphate synthase 1 (CPS1) deficiency, a disorder that hinders the body’s ability to metabolize nitrogen efficiently, resulting in hazardous ammonia accumulation within the bloodstream. Initially confined to a hospital environment and placed on a severely restricted diet, KJ received his pioneering treatment in February 2025 at the age of six to seven months. The therapy was administered without complications, and KJ is now showing healthy growth.
The Inaugural Custom CRISPR Gene Editing Therapy
This innovative treatment marks the world’s first completely customized CRISPR gene editing therapy. This milestone is significant as it illustrates the potential of gene editing technology to effectively target and correct genetic abnormalities in patients lacking existing treatment options for rare genetic disorders. CRISPR technology, renowned for its precision, enables the alteration of specific genetic sequences in the human genome. While this technology has been applied to more prevalent conditions such as sickle cell disease and beta-thalassemia, with FDA-approved therapies already available, many individuals with rare genetic diseases have not been able to benefit from these advancements due to the unique nature of their genetic variations.
In 2023, Dr. Ahrens-Nicklas and Dr. Kiran Musunuru from Penn University initiated a collaborative effort to investigate the feasibility of personalized gene editing therapies. Both researchers are part of the NIH-funded Somatic Cell Genome Editing Consortium and have devoted their careers to studying rare metabolic diseases. Their research focused on urea cycle disorders, which prevent the elimination of ammonia—a byproduct of protein breakdown. In these disorders, the liver lacks the enzymes necessary to convert ammonia into urea, leading to potential damage to the brain and liver.
Encouraging Results
KJ’s genetic disorder was identified shortly after his birth, prompting the research team to develop a mutation-specific treatment within a mere six months. They crafted a base-editing therapy that was delivered to the liver using lipid nanoparticles. KJ received his initial infusion in late February 2025, followed by two additional doses in March and April, all without experiencing any severe side effects. He soon began consuming protein-rich foods and tolerated them well, also managing to recover from common childhood illnesses, such as rhinovirus, without an ammonia spike in his system. While further monitoring is essential to understand the long-term impact, the preliminary results are promising.
Dr. Ahrens-Nicklas expressed optimism about the pioneering therapy, stating, “Although KJ will require lifelong monitoring, our initial outcomes are highly encouraging.” Dr. Musunuru added, “We aspire for every patient to achieve the positive outcomes witnessed in this inaugural patient. We hope other academic researchers will adopt this approach for numerous rare diseases, providing countless patients the opportunity for a healthy life.” “The long-awaited promise of gene therapy is becoming a reality, fundamentally transforming our approach to medicine.”
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