ARPA-H has announced up to USD 160 million in funding over five years for seven performer teams under its THRIVE (Treating Hereditary Rare Diseases with In Vivo Precision Genetic Medicines) program, targeting a structural problem in rare disease drug development: the one-drug, one-disease, one-trial model that makes treatment economics prohibitive for conditions affecting small patient populations.
The program's central innovation is an umbrella clinical trial framework in which a single investigational new drug application accommodates multiple gene editing products and multiple disease phenotypes simultaneously. By year three, performer teams must have initiated first-in-human trials under this model. By year five, teams must demonstrate expanded umbrella INDs and validate novel deployment models for sustainable patient access. Individual awards are milestone-contingent.
The seven funded teams span some of the most active institutions in gene editing and cell therapy research. Children's Hospital of Philadelphia will extend its platform built around kayjayguran abengcemeran — developed for an infant with neonatal-onset CPS1 deficiency — to cover a broader set of rare metabolic and hematological diseases. The University of California, Berkeley's Innovative Genomics Institute will develop in vivo gene editing platforms for inborn errors of immunity, incorporating non-invasive patient identification methods to support real-world deployment. St. Jude Children's Research Hospital will pursue genetic medicines for bone marrow failure disorders using high-sensitivity off-target detection. The Broad Institute will target pediatric epilepsies caused by genetic mutations and develop a novel deployment model for genetic therapies. GEMMABio, supported by Profluent Bio, will apply an AI/ML-based platform to design modular gene editors at scale, with an initial focus including familial hypercholesterolemia. Massachusetts General Hospital will advance non-viral delivery of gene editors to vasculature for rare blood vessel diseases, alongside 3D in vitro vascular models intended to reduce reliance on animal studies. Stanford University will pursue a topical gene editing approach for Epidermolysis Bullosa, a severe genetic skin disorder associated with increased mortality.
The modular platform logic — swapping disease-specific components while preserving common biodistribution and toxicology profiles — is designed to reduce the per-disease cost and timeline of development. Approximately 95% of rare diseases currently lack approved treatments, and pediatric patients with life-threatening genetic conditions represent a population for whom incremental development timelines carry direct clinical consequences.