ARPA-H Makes $27.7 Million Grant to IGI Led Effort to Deliver CRISPR-Based Therapies for IEIs

Rare Daily Staff

The Advanced Research Projects Agency for Health has awarded up to $27.7 million to a multi-institutional team that seeks to transform the treatment of rare pediatric immune disorders with a scalable, lower-cost approach to personalized gene editing.

The team, led by the Innovative Genomics Institute (IGI) at the University of California, Berkeley, will use the funding to support the development of a new platform designed to deliver individualized CRISPR-based therapies for children with inborn errors of immunity (IEIs), a group of rare genetic disorders that affect thousands of newborns in the United States each year.

Despite more than 500 known IEIs, only two currently have approved genetic treatments, each costing more than $1 million per patient and requiring intensive hospital-based procedures. There are no approved in vivo CRISPR therapies or active U.S. clinical trials targeting these conditions.

For children with IEIs and their families, the effort represents a potential path toward safer, faster, and more accessible curative therapies targeting the root cause of disease. If successful, the AEGIS model could redefine how rare genetic diseases are treated—shifting from one-off, high-cost therapies to a repeatable platform capable of rapidly generating individualized medicines.

The newly funded project, known as AEGIS (Affordable Gene Editing Therapies for Immune System Diseases of Children), is part of ARPA-H’s THRIVE program, which focuses on accelerating precision genetic medicines for hereditary diseases. The initiative aims to treat 10 pediatric patients within five years while establishing a platform capable of reducing development timelines for personalized therapies to under three months and lowering costs to below $200,000 per patient.

“The vision is that each child could receive a personalized gene editor delivered via a simple injection, rather than undergoing complex and risky procedures like bone marrow transplantation,” said Donald Kohn, a UCLA physician-scientist and lead principal investigator on the planned clinical trial.

The AEGIS consortium brings together leading clinical and research institutions, including UCLA, the University of Utah’s Primary Children’s Hospital, Mayo Clinic, UC San Diego, Princeton University, Emory University, Stanford University, and industry partner Danaher. The team integrates expertise across gene editing, delivery technologies, clinical care, prenatal diagnostics, and manufacturing.

At the core of the effort is a shift from ex vivo to in vivo gene editing. Current gene therapies for blood and immune disorders typically require harvesting a patient’s stem cells, modifying them outside the body, and reinfusing them following chemotherapy. AEGIS aims to bypass this process by delivering CRISPR-based editors directly to bone marrow stem cells using engineered lipid nanoparticles.

The program will also expand the range of treatable mutations by combining multiple gene editing approaches. Base editing, advanced through foundational work by UC San Diego’s Alexis Komor, and prime editing, led by Princeton’s Britt Adamson, will be deployed in parallel to address a broader set of genetic variants underlying IEIs.

Fyodor Urnov of UC Berkeley and IGI, a pioneering figure in the development of CRISPR-based therapeutics, leads AEGIS. He said the field has reached an inflection point.

“We now have the tools, the clinical expertise, and growing regulatory momentum,” said Urnov. “This program brings those pieces together into a platform where no child is left behind due to the specific mutation they carry.”