ARPA-H THRIVE Awards $73.4 Million to Advance Personalized Gene-Editing Platforms for Rare Pediatric Diseases
核心洞察
Children's Hospital of Philadelphia received up to $38.9 million over five years to develop personalized gene-editing therapies for four groups of rare liver-related genetic disorders, including urea cycle disorders (搜索) and hemophilia A (搜索).
The Jackson Laboratory and Broad Institute (搜索) secured up to $34.5 million for the PERC platform targeting pediatric epilepsies, initially focusing on alternating hemiplegia of childhood (搜索) and Dravet syndrome (搜索).
Both awards come through ARPA-H (搜索)'s THRIVE initiative, which aims to transform individualized gene-editing approaches into scalable, repeatable platforms for rare disease treatment.
The Advanced Research Projects Agency for Health (ARPA-H (搜索)) has awarded a combined total of up to $73.4 million across two major initiatives aimed at transforming personalized gene-editing therapies into scalable platforms for children with rare, life-threatening genetic disorders. The awards, announced July 9, 2026, come through ARPA-H's Treating Hereditary Rare Diseases with In Vivo Precision Genetic Medicines (THRIVE) program, led by Program Manager Daria Fedyukina, Ph.D.
Children's Hospital of Philadelphia (CHOP) secured a five-year award of up to $38.9 million, while The Jackson Laboratory (JAX), in partnership with the Broad Institute (搜索) and other collaborators, received an up to $34.5 million contract. Together, the programs represent a coordinated federal effort to move beyond one-off personalized treatments toward reproducible platforms capable of addressing multiple rare diseases.
CHOP Targets Four Liver-Related Genetic Disorder Groups
The CHOP-led program builds on the landmark treatment of baby KJ Muldoon, whose first-ever personalized gene-editing therapy was led by Rebecca Ahrens-Nicklas, MD, PhD, and Kiran Musunuru, MD, PhD, MPH, ML, MRA. The new award will focus on developing individualized gene-editing therapies for four groups of rare, liver-related genetic disorders: urea cycle disorders (搜索), characterized by dangerous newborn ammonia buildup; organic acidemias (搜索), which cause toxic metabolites and metabolic crises in infants; severe blood clotting disorders such as protein C deficiency (搜索); and bleeding disorders including hemophilia A (搜索).
"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 Ahrens-Nicklas, Director of CHOP's Gene Therapy for Inherited Metabolic Disorders Frontier Program. "Formal clinical trials are needed to evaluate if gene editing therapies are safe and if they work."
The five-year plan is organized into three core components: building and refining base editing and prime editing lipid nanoparticle systems to create reliable tools for precise gene correction; conducting clinical trials and pursuing regulatory approvals; and engaging payers while expanding treatment access through community sites and remote hubs.
Lindsey A. George, MD, CHOP's Director of Clinical In Vivo Gene Therapy, added: "We are excited to pursue this work and to contribute to the broader goal of advancing the development of transformative individualized gene editing therapies."
PERC Platform Targets Pediatric Epilepsies and CNS Disorders
The second award supports the Pediatric Epilepsies & Rare CNS (PERC) Gene Editing Platform, a multi-institutional project led by the Broad Institute (搜索) with JAX, Boston Children's Hospital, the RARE Hope Foundation, and other partners across 12 institutions and organizations.
PERC will initially focus on two severe pediatric developmental and epileptic encephalopathies: alternating hemiplegia of childhood (搜索) (AHC) and Dravet syndrome (搜索). The project pursues three core objectives: advancing gene-editing approaches for both conditions, generating evidence needed to move toward first-in-human studies, and building a reproducible, repeatable platform and regulatory pathway scalable to additional rare neurogenetic diseases.
"PERC gives us an opportunity to stop thinking about each rare disease program as something that has to start from scratch and instead build a process that is more systematic, repeatable, and adaptable," said Cathleen (Cat) Lutz, PhD, MBA, Vice President and Evnin Family Chair of the Rare Disease Translational Center at JAX.
Rare diseases collectively affect hundreds of millions of people worldwide, with children disproportionately impacted. Roughly half of known rare genetic diseases involve the central nervous system, and 90% of rare childhood disorders have major neurological effects. Children with these conditions often experience severe neurologic impairment and high mortality before age five.
The conventional drug development model is poorly suited to rare and ultra-rare diseases affecting small populations. For rare CNS diseases, therapies must cross the blood-brain barrier, demonstrate safety and efficacy in rigorous preclinical models, navigate regulatory review, and be evaluated in small patient populations where traditional clinical trial designs may not apply.
Winston Yan, MD, PhD, Co-founder and Director of the Center for Therapeutic Genetics and Lead Investigator for PERC at the Broad Institute (搜索), noted: "With support from ARPA-H (搜索), we have an opportunity to help establish new treatments for patients affected by AHC and Dravet syndrome (搜索), while also building a platform that can be extended to additional rare neurologic diseases."
A Broader Federal Push
The awards are part of a broader federal effort to strengthen U.S. leadership in clinical research. In June, HHS announced a coordinated initiative to modernize clinical research, reduce delays, increase trial participation, and ensure that next-generation medical breakthroughs are developed domestically. THRIVE was cited as a major ARPA-H (搜索) initiative within that effort, focused on testing multiple treatments and diseases simultaneously while improving trial efficiency before patient enrollment begins.