The U.S. Advanced Research Projects Agency for Health (ARPA-H) announced July 9 that it will commit up to $160 million over five years to develop a new model for treating rare genetic diseases: custom, in vivo gene editing drugs made for individual patients or small groups sharing the same mutation.
The program, called THRIVE (Treating Hereditary Rare Diseases with In Vivo Precision Genetic Medicines), will fund seven research teams across the United States. It aims to transform bespoke gene therapies from one-off medical miracles into a scalable, regulated treatment paradigm.
“The goal is to go from saving one Baby KJ to saving thousands,” an ARPA-H official said in the announcement, referencing a case that has become the program’s defining parable.
The Baby KJ Paradigm
In February 2025, a 7-month-old boy named KJ Muldoon of Clifton Heights, Pennsylvania, became the first person ever to receive a systemic, personalized in vivo CRISPR gene editing drug. KJ was born with severe neonatal-onset CPS1 deficiency, a urea cycle disorder affecting roughly 1 in 1.3 million infants, in which the body cannot clear ammonia from the blood. Half of affected babies die.
Researchers at Children’s Hospital of Philadelphia (CHOP) and the University of Pennsylvania created kayjayguran abengcemeran, a custom base editor delivered via lipid nanoparticles targeting KJ’s specific CPS1 mutation. The result: KJ’s severe form was converted to a milder one. He was discharged after 307 days in the hospital. Nature named him to its “10 people who shaped science in 2025” list.
But the effort that saved KJ cost roughly $25 million and took four years. THRIVE aims to compress that to $250,000 and three months per patient.
The Seven Teams
The seven awardees and their targets span a wide range of rare diseases:
| Lead Organization | Target Diseases |
|—————–|—————–|
| Children’s Hospital of Philadelphia | Neonatal-onset CPS1 deficiency and other urea cycle disorders, building on the Baby KJ platform |
| UC Berkeley / Innovative Genomics Institute | Life-threatening inborn errors of immunity |
| St. Jude Children’s Research Hospital | Bone marrow failure disorders |
| Broad Institute (with Jackson Laboratory) | Pediatric epilepsies, Alternating Hemiplegia of Childhood and Dravet syndrome |
| GEMMABio (with Profluent Bio) | Diseases causing extreme cholesterol levels |
| Massachusetts General Hospital | Rare genetic diseases of blood vessels |
| Stanford University | Epidermolysis Bullosa (fragile skin disorder) |
A companion program, GIVE (Genetic Medicines and Individualized Manufacturing for Everyone), funds decentralized manufacturing infrastructure, including work toward placing automated production units in hospitals.
A Five-Year Roadmap
THRIVE is structured with milestone gates. Year 1 focuses on demonstrating that gene editing platforms can generate multiple drug products sharing common biodistribution and toxicology profiles. By Year 3, the program aims to begin first-in-human umbrella clinical trials, single trials accommodating several drug products and disease phenotypes simultaneously. By Year 5, the program aims to have expanded umbrella INDs with additional drug products and validated novel deployment models.
Funding per team varies and is contingent on meeting milestones. The Broad Institute’s sub-award to Jackson Laboratory, for example, is up to $34.5 million alone.
A New Regulatory Pathway
THRIVE depends on a new regulatory framework the FDA proposed in draft guidance in February 2026: the “plausible mechanism” pathway. Under this framework, a therapy targeting a specific molecular abnormality with a known biological cause can move forward on a single hybrid proof-of-concept study, using external controls instead of placebos and master protocols allowing multiple mutations in one trial.
Under existing rules, each bespoke CRISPR therapy costs $25 million and takes four years. Under the plausible mechanism framework, estimates drop to $250,000 and approximately three months per patient.
Critics and experts have noted significant execution risks. Manufacturing bespoke therapies at scale, especially through decentralized models, poses major technical hurdles in demonstrating site-to-site product comparability. Regulatory consistency across rare disease programs also remains an open question. But the framework has been broadly welcomed by patient advocacy groups, and the THRIVE program represents the largest government investment yet in making individualized gene editing a clinical reality.
Source: “ARPA-H launches $160 million effort to develop custom gene editing drugs.” STAT News, July 9, 2026. https://www.statnews.com/2026/07/09/arpa-h-160-million-custom-gene-editing-funding-rare-disease/