The Children’s Hospital of Philadelphia has received an award of up to $38.9 million from the Advanced Research Projects Agency for Health to develop personalized gene-editing therapies for four rare genetic disorders, including hemophilia. According to a hospital press release, the five-year funding comes through the agency’s THRIVE program, which focuses on precision genetic medicines for hereditary conditions.
ARPA-H THRIVE Program Funds CHOP Research Team
The research is led by Rebecca Ahrens-Nicklas, MD, PhD, who directs the gene therapy for inherited metabolic disorders Frontier program at CHOP, alongside Lindsey A. George, MD, director of clinical in vivo gene therapy. Kiran Musunuru, MD, PhD, codirector of the Orphan Disease Center—a joint program between CHOP and Penn Medicine—is also part of the team. The broader THRIVE program is managed by Daria Fedyukina, PhD, according to CHOP.
This initiative expands upon the treatment of KJ Muldoon, an infant born in 2024 with carbamoyl phosphate synthetase 1 deficiency. That case marked the first personalized gene-editing therapy, which was developed by the same CHOP team of Ahrens-Nicklas and Musunuru.
Targeting Rare Liver-Related Genetic Disorders in Children
The new funding extends custom treatments to four rare, liver-related genetic conditions affecting infants and children. These include hemophilia A, severe blood-clotting conditions like protein C deficiency, urea cycle disorders that prevent the body from properly clearing ammonia, and organic acidemias caused by the toxic buildup of metabolites.
“Current care for these patients typically requires lifelong special diets, regular infusions, or liver transplants, which carry big risks and delays,” Ahrens-Nicklas said. “Tragically, many infants die or have major morbidity before a treatment is possible.” She added that formal clinical trials remain necessary to evaluate the safety and effectiveness of these gene-editing approaches.
Did you know?
In hemophilia A, patients carry mutations in the F8 gene, which provides instructions for making factor VIII, a key blood-clotting protein produced primarily in the liver. Gene-editing strategies aim to insert a working copy of this gene into liver cells to restore natural clotting function.
Three-Part Plan for Scalable Gene-Editing Delivery
The five-year research plan relies on three core steps. First, the team will build and refine lipid nanoparticle delivery systems for base editing and prime editing, two techniques that allow precise DNA corrections. Second, the researchers will conduct clinical trials for patients with the four target disorders. Third, the team will pursue regulatory approval, coordinate with insurance payers, and work to expand access so treatments can reach community sites and remote hubs rather than remaining confined to a single academic center, according to CHOP.
“We are excited to pursue this work and to contribute to the broader goal of advancing the development of transformative individualized gene editing therapies,” George said.
Frequently Asked Questions
What conditions will the new CHOP funding target?
The funding targets four rare, liver-related genetic disorders in infants and children: hemophilia A, protein C deficiency, urea cycle disorders, and organic acidemias.
Where is the funding coming from?
The five-year award comes from the Advanced Research Projects Agency for Health under its THRIVE program.
What gene-editing techniques are researchers using?
The team is utilizing base editing and prime editing delivered via lipid nanoparticle systems to make precise DNA corrections.