Federal Project Grant Award Summary

The National Institute of Neurological Disorders and Stroke (NINDS) awarded the University of California, Davis a Project Grant of $442,750 under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, effective April 1, 2026, through March 31, 2028. The research initiative focuses on optimizing adeno-associated viral (AAV) gene therapy delivery to the central nervous system through high-throughput screening of novel inverted terminal repeat (ITR) domains in the mouse brain. AAV vectors represent the current gold standard for genetic cargo delivery to the brain; however, transgene expression remains a critical limitation despite advances in transduction efficiency and biodistribution.

The project deliverables include identification and characterization of ITR domains that enhance transgene expression beyond naturally occurring ITR sequences currently used in AAV gene therapy platforms. Through library screening in mouse brain models, the research aims to identify optimized ITR variants that outperform both conventional ITR and self-complementary ITR approaches. Additionally, the grant supports investigation of novel mechanisms to enhance AAV particle production and secretion into extracellular space, with the ultimate objective of advancing AAV gene therapy efficacy for clinical applications in treating neurological and neuromuscular disorders.