Celebrating a Year of Breakthroughs: The Impact of CRISPR Therapy at CHOP

February 25, 2026, marks a significant milestone in gene therapy history—the first anniversary of KJ Muldoon's groundbreaking treatment at the Children's Hospital of Philadelphia (CHOP). This moment captures not only the hopes of one child but also the collective aspirations of the medical community for pioneering advancements in genetic disease management.

KJ, diagnosed with a rare metabolic disorder known as severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, became the world's first patient to receive a personalized CRISPR-based gene editing therapy, a monumental achievement developed by dedicated physician-scientists at CHOP and Penn Medicine. This innovative treatment, tailored specifically to address KJ's unique genetic condition, was safely administered after promising preclinical studies and extensive collaboration among researchers and professionals leading to its advent.

Dr. Rebecca Ahrens-Nicklas, Director of CHOP's Gene Therapy for Inherited Metabolic Disorders Program, expressed her excitement about KJ's progress. Following three successful infusions from February to April 2025, KJ has shown astonishing clinical improvements. He has begun to walk and talk, illustrating the potential of gene therapy to enable children with rare conditions to lead healthier lives. Although not a complete cure, this therapy has allowed KJ to tolerate higher levels of dietary protein and manage ammonia levels more effectively, demonstrating its significant impact on his daily life.

KJ's journey represents the culmination of decades of meticulous research and the synergy between clinical care and scientific exploration. The personalized gene therapy, which involved base editing delivered via lipid nanoparticles to correct KJ's CPS1 gene variant in the liver, exemplifies CHOP’s commitment to combining advanced research with patient care that directly caters to children's needs. Currently, the institution supports over 80 faculty members engaged in cell and gene therapy research, driving more than 45 active pediatric clinical trials targeting various genetic disorders.

Dr. Kiran Musunuru, Co-Director of the Orphan Disease Center (ODC), highlights the burgeoning potential of gene editing in pediatrics. Aiming for broader applications of these revolutionary therapies, the team is not only developing better treatments for individual patients but is also creating frameworks for umbrella clinical trials designed to expedite the process of bringing therapies to more patients, thereby broadening their accessibility.

In a recent trip to Washington, D.C., KJ and his parents shared their story with lawmakers, emphasizing the invaluable nature of personalized gene therapies for families dealing with rare diseases. Kyle Muldoon, KJ's father, expressed a heartfelt desire to humanize the challenges faced by those with rare conditions, while Nicole Muldoon, his mother, echoed the sentiment that all children should have the chance to benefit from modern medical advancements.

The journey of KJ and CHOP is setting in motion essential discussions about new approval models for personalized therapies. Recently, the FDA introduced a new framework aimed at accelerating the approval process for individualized treatments—a monumental development for the community of patients with rare genetic disorders. This framework would treat variant-specific versions of a gene editor as a single entity, simplifying the review process and facilitating faster access to vital treatments for countless children in need.

As CHOP dives deeper into researching methods for treating hard-to-manage metabolic conditions through its Gene Therapy for Inherited Metabolic Disorders Program, KJ's case stands as a beacon of hope that will potentially influence approval guidelines and lead to more personalized therapies reaching patients sooner.

CHOP’s commitment to transforming healthcare is evident as it continues to lead the way in pediatric research and care, influencing policies to ensure access to cutting-edge therapies. The road ahead looks promising, with dedicated professionals striving to offer every child the chance to thrive against the odds brought on by rare diseases.

The Children's Hospital of Philadelphia exemplifies the merging of compassionate patient care with scientific innovation, ushering in a new era of possibilities in pediatric medicine. To learn more about their ongoing efforts and research initiatives, visit CHOP’s official website.