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ARPA-H Awards $160 Million to Seven Teams to Build Scalable Gene-Editing Platforms for Rare Pediatric Diseases

ARPA-H's new THRIVE program is funding seven teams to build reusable gene-editing platforms for rare pediatric diseases, aiming to move beyond one-patient-at-a-time therapies like the one made for infant KJ Muldoon.

Biotech & Medicine Gene Therapy
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Overview

The Advanced Research Projects Agency for Health (ARPA-H) announced on July 9 that it has selected seven teams to build reusable, scalable gene-editing platforms for rare pediatric genetic diseases, committing up to $160 million over five years to a new initiative called THRIVE — Treating Hereditary Rare Diseases with In Vivo Precision Genetic Medicines. The program is designed to move gene editing away from bespoke, one-patient therapies and toward platforms that can be adapted across many diseases at once, according to ARPA-H.

What We Know

The program

ARPA-H, an agency within the U.S. Department of Health and Human Services, said the awards target diseases for which, according to the agency, “about 95% of rare diseases have no approved medicines” under a traditional model built around one drug, one disease, and one clinical trial at a time.

“By transforming precision genetic medicines through platforms that can test multiple treatments for multiple diseases in a single clinical trial, THRIVE reflects the kind of groundbreaking health innovation needed to help children and families facing life-threatening genetic diseases,” said Alicia Jackson, Ph.D., ARPA-H Director.

THRIVE Program Manager Daria Fedyukina, Ph.D., described the shift away from the legacy model: “Our current system is built to develop one drug for one disease tested in clinical trials designed specifically for that drug and that disease. Patients with rare genetic diseases, especially children, cannot wait for this legacy approach, it’s too slow and unsustainable,” she said, according to ARPA-H. In a separate interview with Boston Globe/STAT, Fedyukina put the program’s ambition more bluntly: “How can we build a paradigm that is also sustainable and can treat thousands of babies?”

Each team faces the same milestone structure, per ARPA-H: in year one, teams must demonstrate gene-editing platforms capable of generating multiple drug products with shared biodistribution and toxicology profiles; by year three, they must begin first-in-human trials that, for the first time, accommodate several different products and disease phenotypes under one umbrella trial; and by year five, they must expand that umbrella investigational new drug application to additional products and diseases.

The seven teams

ARPA-H named the awardees and their disease targets in its announcement:

  • Children’s Hospital of Philadelphia (CHOP) — rare metabolic and hematological diseases caused by pathogenic mutations
  • University of California, Berkeley / Innovative Genomics Institute — inborn errors of immunity, paired with a rapid non-invasive patient identification method
  • St. Jude Children’s Research Hospital — bone marrow failure disorders
  • The Broad Institute — pediatric epilepsies caused by genetic mutations
  • GEMMABio, supported by Profluent Bio — an AI/ML-based platform for modular gene editors, targeting genetic diseases including extreme inherited cholesterol levels
  • Massachusetts General Hospital — rare genetic diseases of blood vessels, including non-viral delivery methods and 3D vascular models to speed testing
  • Stanford University — Epidermolysis Bullosa, a group of rare skin diseases, using a topical gene-editing approach

GEMMABio is run by gene therapy pioneer Jim Wilson, according to Boston Globe/STAT.

A closer look: $34.5 million for pediatric epilepsy

The only individual award amount disclosed so far belongs to the Broad Institute-led team. The Jackson Laboratory (JAX) said it has been selected, alongside the Broad Institute and other partners, for an up to $34.5 million contract to fund the Pediatric Epilepsies & Rare CNS (PERC) gene-editing platform, which will initially focus on two conditions: alternating hemiplegia of childhood (AHC) and Dravet syndrome, according to JAX.

“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, vice president and Evnin Family Chair of the Rare Disease Translational Center at The Jackson Laboratory.

Dr. Winston Yan, co-founder and director of the Center for Therapeutic Genetics and lead investigator for PERC at the Broad Institute, said the project “builds on a longstanding collaboration among the Broad Institute, The Jackson Laboratory, Boston Children’s Hospital, RARE Hope, and other partners,” according to JAX. The PERC coalition spans 12 institutions and organizations and will integrate base editing, prime editing, and in vivo delivery of genetic therapies to the brain, JAX said. The stakes for CNS-focused rare diseases are steep: JAX cited research published in The Lancet Neurology finding that roughly half of known rare genetic diseases involve the central nervous system, and 90% of rare childhood disorders have major neurological effects.

The precedent behind the program

CHOP’s award explicitly builds on prior work: ARPA-H said the Philadelphia team “will build upon teams’ success in developing” a personalized gene-editing therapy “made for an infant with a severe UCD (neonatal-onset CPS1 deficiency),” according to ARPA-H — a reference to KJ Muldoon, the infant previously reported to have received the first personalized CRISPR gene-editing therapy, created at CHOP for his urea cycle disorder. Boston Globe/STAT, republishing STAT News reporting, noted that KJ’s treatment “was a stunning demonstration of the power of new genetic tools to fix even the rarest of mutations, but it was not readily scalable. It required a vast team and a company willing to write off the immense expense. No one has said how much it cost,” according to Boston Globe/STAT. THRIVE is intended to turn that kind of one-off effort into a repeatable process.

A program years in the making

Word of the program “began circulating around 2024,” and over 100 groups applied for funding, according to Boston Globe/STAT. Funding was approved in early 2025 by former ARPA-H director Renee Wegrzyn, but the program’s original director, Mimi Lee, said its launch was delayed by a change in presidential administrations. “Shortly thereafter, she was asked to leave and agency program launches were largely put on hold while the administration introduced new approval processes and a new director could be installed,” Lee said in an email, adding: “Luckily, we were able to engage productively with HHS leadership who supported releasing THRIVE, one of less than a handful of programs released during the nine-month leadership gap,” according to Boston Globe/STAT. Lee left ARPA-H last October, saying she had received an opportunity to make a larger impact outside the agency.

The program that emerged is narrower than Lee’s original vision, which would have covered a broader suite of genetic technologies. “There was originally some hope that it could really move the field more than just a couple years,” said Erik Sontheimer, a gene-editing researcher at the UMass Chan Medical School. Sontheimer also cautioned that teams targeting harder-to-reach organs such as skin or brain are likely further from success than others: “Skin would certainly be a big step,” he said, according to Boston Globe/STAT.

Fedyukina declined to dwell on the program’s history, saying she hopes that within five years, a majority of teams will have demonstrated proof-of-concept for their diseases and a path toward sustainable development of custom treatments. “We are going to maximize the value for the budget that I have,” she said. “And the way I’m going to run this program is going to be extremely practical, because I want results,” according to Boston Globe/STAT.

What We Don’t Know

ARPA-H has not disclosed how the rest of the $160 million commitment is split among the other six teams beyond the $34.5 million confirmed for the Jackson Laboratory/Broad Institute award. It also remains unclear whether teams working on harder-to-reach organs, such as the brain and skin, will meet the same year-three clinical trial deadline as teams with more established delivery methods, or how the FDA’s regulatory review of these platform-based, multi-disease trials will ultimately be structured.