Award topping $35M to fuel CHOP gene editing work in hemophilia A

Children’s Hospital of Philadelphia (CHOP) has been awarded up to $38.9 million to advance the development of personalized gene‑editing therapies for four groups of rare genetic disorders — one of them hemophilia.

The five-year award comes from the Advanced Research Projects Agency for Health (ARPA‑H) under its THRIVE program, which aims to treat hereditary conditions using precision genetic medicines. The funding will support work led by Rebecca Ahrens-Nicklas, MD, PhD, director of CHOP’s gene therapy for inherited metabolic disorders Frontier program, and Lindsey A. George, MD, CHOP’s director of clinical in vivo gene therapy.

The team also includes Kiran Musunuru, MD, PhD, codirector of the Orphan Disease Center, a joint program between CHOP and Penn Medicine. The THRIVE program itself is overseen by ARPA-H program manager Daria Fedyukina, PhD, according to a CHOP press release announcing the new funding.

This award builds on the widely reported case of KJ Muldoon, an infant born in 2024 with a severe rare disease known as carbamoyl phosphate synthetase 1 (CPS1) deficiency. He received the first personalized gene-editing therapy, developed by the same CHOP team of Ahrens-Nicklas and Musunuru.

The new funding will extend that work to four rare, liver-related genetic disorders in infants and children. This includes the bleeding disorder hemophilia A, as well as severe blood-clotting conditions, such as protein C deficiency, and urea cycle disorders, in which the body cannot properly clear ammonia. It also covers work in organic acidemias, which are caused by the toxic buildup of metabolites.

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“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.”

To better treat these patients, the scientists are working to develop personalized treatments targeted to their specific diseases.

Ahrens-Nicklas noted that formal clinical trials are still needed to determine whether gene-editing approaches are both safe and effective for these patients.

3-part plan set to advance these gene-editing treatments

The five-year research plan has three main parts. First, the CHOP team will build and refine lipid nanoparticle delivery systems for two gene-editing techniques: base editing and prime editing. These techniques allow scientists to make precise, targeted corrections to DNA.

Second, the team will conduct clinical trials to test these individualized therapies in patients with the four target disorders. And third, the scientists will work on regulatory approval, engage with insurance payers, and seek to expand access to treatment. The goal is to bring these therapies to community sites and remote treatment hubs, rather than limiting availability 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.

The project’s overall aim is to move from a one-off, customized treatment approach, like the one used in the Muldoon case, toward a repeatable and scalable platform that can be applied across multiple rare liver-related genetic diseases while addressing the safety, manufacturing, and access challenges that come with personalized medicine.

George described the broader goal of the effort, saying, “We are excited to pursue this work and to contribute to the broader goal of advancing the development of transformative individualized gene editing therapies.”

Hemophilia is most often caused by genetic mutations that reduce the production or function of key blood-clotting proteins. This leads to the disease’s characteristic symptoms: bleeding episodes that are excessive, prolonged, or occur without any clear trigger.

Because hemophilia has a known genetic cause, gene editing has become a therapeutic strategy of significant interest for this disease and others. This approach works by modifying a person’s DNA to address the underlying cause of the disease.

In hemophilia A, for instance, patients carry mutations in the F8 gene, which normally provides instructions for a clotting protein called factor VIII (FVIII), made primarily in the liver. A gene-editing approach for these patients might aim to insert a working copy of the F8 gene into their liver cells to restore the body’s ability to produce functional FVIII.