Children’s Hospital of Philadelphia (CHOP) has secured a five-year, up to $38.9 million award from the Advanced Research Projects Agency for Health (ARPA-H) to accelerate the development of personalized gene-editing therapies for children born with rare, life-threatening liver-related genetic diseases.
The funding, awarded through ARPA-H’s THRIVE program, will support a CHOP-led effort to turn the promise of individualized gene editing into a repeatable treatment approach for patients who currently have few options beyond lifelong medical interventions or organ transplantation.
The award builds on CHOP’s landmark achievement in developing the world’s first personalized gene-editing therapy for baby KJ Muldoon, whose treatment was led by Ahrens-Nicklas and Musunuru.
The new initiative will expand that approach to four major categories of rare liver-related genetic disorders: Urea cycle disorders, which can cause dangerous ammonia buildup in newborns; Organic acidemias, which lead to toxic metabolite accumulation and metabolic crises; Severe blood clotting disorders, including protein C deficiency; Bleeding disorders, including hemophilia A.
The CHOP-led team will develop advanced base editing and prime editing lipid nanoparticle systems designed to precisely correct disease-causing genetic mutations. Researchers will also conduct clinical trials, seek regulatory approvals, work with payers, and establish pathways to deliver treatments through community sites and remote hubs.
"Current care for these patients typically requires lifelong special diets, regular infusions, or liver transplants, which carry big risks and delays. Tragically, many infants die or have major morbidity before a treatment is possible,” said Rebecca Ahrens-Nicklas, the program lead. “Formal clinical trials are needed to evaluate if gene editing therapies are safe and if they work.”
The five-year project is designed to address the scientific, regulatory, manufacturing, and access challenges involved in bringing personalized gene-editing therapies from the laboratory to children who need them most.
