Federal Project Grant Award Summary

The University of Massachusetts Medical School received a $1.675 million Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859) for the period May 1, 2026 through April 30, 2030. This research project investigates the roles of truncated and mutated inverted terminal repeat (ITR) sequences in adeno-associated virus (AAV) vectors and their impact on transgene stability through episome formation and host cell genome integration. The research addresses critical safety considerations in AAV-based gene therapies, which have emerged as transformative treatments for human genetic diseases, by examining how structural variations in ITR sequences—the only viral elements retained in therapeutic AAV vectors—influence the frequency and outcomes of vector integration into host cell genomes.

The three-aim project will deliver fundamental scientific knowledge through advanced next-generation sequencing-based analysis and characterization of ITR structures in wildtype AAVs and manufactured gene therapy vectors. Specifically, the research will examine how ITR integrity affects integration frequency and outcomes, establish mechanistic understanding of truncated and mutated ITR functions, and translate findings to optimize AAV vector design and manufacturing for enhanced safety and therapeutic efficacy. The research will be conducted at UMMS's Worcester, Massachusetts facility and will generate peer-reviewed publications and technical findings intended to paradigm-shift understanding of AAV-based gene therapy applications and inform regulatory and manufacturing standards for this critical therapeutic platform.