Federal Grant Award Summary

The Broad Institute of MIT and Harvard received a $404,282 Project Grant from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853), awarded on May 1, 2026, with completion scheduled for April 30, 2028. The research focuses on engineering transferrin receptor 1 (TFR1)-binding adeno-associated virus (AAV) capsids capable of evading pre-existing neutralizing antibodies (NAbs) while maintaining enhanced blood-brain barrier (BBB) penetration for central nervous system (CNS) gene therapy delivery. The Broad Institute will develop next-generation AAV capsids that overcome a significant limitation of current AAV-based gene therapies—the presence of NAbs in 40-80% of the population—which currently restricts patient eligibility for transformative neurological disease treatments.

The deliverables under this award include engineered TFR1-binding AAV capsid variants that achieve NAb evasion in the majority of patient populations while preserving CNS tropism enhancement and manufacturing scalability. Using established and novel screening assays, the research team will advance preliminary capsids that have demonstrated full NAb evasion in over 40% of human sera samples containing antibodies that neutralize AAV9 and AAV5. This work directly supports NINDS's mission to reduce the burden of neurological disease by expanding the therapeutic applicability of AAV gene therapies for severe CNS disorders currently lacking disease-modifying treatment options.