The BRAIN-STORRM Network for AAV vector manufacture and distribution

Cell type specific neural circuits are the foundation of adaptive behaviors and cognitive functions, including learning, memory, and decision making. Therefore, identifying cell type specific neurocomputational principles is a primary goal of the BRAIN Initiative and of our research program. A crucial tool in nearly all studies of cell type specific neural circuits is adeno associated viral (AAV) vectors. To diversify research into neural circuits, and to expand access to underrepresented groups and more neuroscience labs, we propose to establish the BRAIN-STORRM (Scientific and Technical Operations for Resource/Reagent Manufacturing) Center at the HBCU University of Maryland Eastern Shore (UMES). The BRAIN-STORRM Center at UMES will be a vector core and validation site that is closely integrated with a major effort at the University of Pittsburgh (UF1MH130881) to develop cell type specific AAVs. The resulting BRAIN-STORRM Network has three principal goals: (1) Complement and expand the UF1 work, which is focused on creating and validating enhancer-driven AAVs that are cell type specific in nonhuman primates, by validating AAV cell type specificity in wild type mice; (2) Test and validate the effectiveness of cell type specific enhancers in different AAV capsids with various delivery routes, and thereby build a catalog of ready-to-ship vectors, each with multiple payload options, including GFP, optogenetic, chemogenetic, and calcium sensor transgenes; and (3) Train a new generation of scientists from underserved populations in cutting edge molecular biology techniques, with expertise in AAV technology, and prepare them for academic and biotechnology careers. A web-based inventory will catalog availability and enable easy ordering, and constructs will be distributed under a modest cost-recovery structure. The BRAIN-STORRM Center will scale up production, availability, and distribution of cell type specific AAV-enhancer vectors and provide a vital resource for these high-demand biologicals. Its work validating enhancers in multiple serotypes is critical science that will expand resource access to labs working in rodents and provide UMES students with the opportunity to publish high impact papers and launch their careers. These capacity-building efforts will enhance the impact of BRAIN Initiative funded research and tool development, diversify participation, and increase the pace, scope, and quality of neuroscientific discovery.