The Advanced Research Projects Agency for Health (ARPA-H), under its Health Science Futures Office, has released the THRIVE Innovative Solutions Opening (ISO), focused on developing in vivo precision genetic medicines for hereditary rare diseases. ARPA-H’s mission is to accelerate transformative biomedical innovations that address pressing health challenges. THRIVE specifically aims to change the paradigm of rare disease treatment by supporting one-time therapeutic interventions capable of slowing, reversing, or curing conditions that collectively affect one in ten individuals, despite their individually small populations.
The THRIVE program responds to the unmet medical needs of more than 30 million Americans, most of whom are children, infants, and newborns, who currently lack therapeutic options for rare diseases. Unlike conventional gene therapies relying on viral delivery or ex vivo methods, THRIVE explicitly excludes adeno-associated virus (AAV)-mediated transgene supplementation and first-generation CRISPR-Cas9 approaches. Instead, it seeks new platforms combining therapeutic cargoes—such as base editors, gene insertion technologies, or antisense oligonucleotides—with precision delivery tools like synthetic nanoparticles. These integrated platforms should be able to target multiple variants, clusters of mutations, or diseases with common genetic pathways.
The program is structured as a five-year effort with three modules. Module 1 funds platform design and development, requiring teams to advance multiple precision genetic medicine (PGM) platforms that demonstrate safety and potential efficacy. Module 2 moves successful candidates to investigational medicine, allowing patient trial participation under strict regulatory and ethical oversight. Module 3 scales solutions by piloting treatment delivery through expert hubs and satellite clinics more than 250 miles away, ensuring broader geographic access. Long-term patient monitoring of at least 15 years is mandated. A federated THRIVE data platform will consolidate findings from program performers, regulators, and external partners to enable machine learning-assisted therapeutic iteration.
Proposals must be submitted by multidisciplinary teams including patient advocacy leaders, academic researchers, and industry partners. Teams must enter into a Multi-Party Teaming Agreement (MPTA) and include a dedicated Project Manager/Integrator. ARPA-H awards will be made through Other Transaction (OT) agreements, with cost sharing required: 0% in year one, rising annually to 80% by year five. AAV-related costs will be supported at no more than 20%, requiring additional non-federal contributions.
Key deadlines include a solution summary due by October 31, 2025, and full proposals due December 19, 2025. A virtual Proposers’ Day, lightning talks, and sidebar meetings will support team formation. The program will make multiple awards, with proposal evaluation emphasizing technical merit, contribution to ARPA-H’s mission, proposer capabilities, and cost realism. The official program contact is THRIVE@arpa-h.gov. The THRIVE ISO represents a high-risk, high-reward opportunity to build scalable infrastructure and therapies that could permanently shift healthcare for patients living with rare genetic diseases.
Focus on transformative innovation; address cost, manufacturability, and product quality; avoid incremental improvements or inflated budgets
