Viral Innovation Core

University Of Minnesota, Minneapolis MN

Investigators

Linked publications, trials & patents

Abstract

PROJECT SUMMARY: Viral Innovation Core Viral vectors are used extensively in neuroscience research to deliver an ever-expanding toolkit of genetically encoded reagents that can disrupt or modify gene expression, control the excitability of cells within circuits, identify connections within and across brain regions, and help visualize real-time indices of cellular activity and neurotransmission with spatial and temporal precision. Adeno-Associated Virus (AAV) vectors are commonly used for this purpose given their broad tropism, ability to promote stable gene expression, and low cytotoxicity and immunogenicity profiles. AAV vectors are used by many investigators within the University of Minnesota (UMN) addiction research community. The demand for AAV vector production within this group has grown steadily since the founding of the UMN Viral Vector and Cloning Core (VVCC) in 2017, driven in large part by faculty hiring in the addiction neurosciences and NIH/NIDA support for the Center for Neural Circuits in Addiction and its Viral Innovation Core/VIC. The goal for the VIC in the next funding period is to sustain its positive impact by meeting the expanding AAV vector needs of the UMN addiction research community. The mission of the VIC is encapsulated in two AIMs: 1) Generating AAV vectors to support the UMN addiction research community. In the initial project period, the VIC exceeded critical benchmarks related to AAV production, while also fueling the development and optimization of a pipeline of advanced vector characterization assays to evaluate AAV vector quality. In the next funding cycle, the VIC will build on its positive impact by increasing its support for AAV vector generation – including custom vectors that are in high demand – for the growing UMN addiction research community. Centralization of AAV production represents a critical efficiency for Center Investigators and Affiliates, many of whom apply these tools to projects supported by other Research Cores. 2) Special Projects: Engineering tropism of AAV. In the initial project period, the VIC supported research into the “engineerable capacity” of the AAV backbone. We were successful in identifying new capsid regions and strategies for adding binding scaffolds (e.g., nanobodies) without impairing virus yield, post-entry steps, and infectivity. In the next funding cycle, the VIC will leverage these new opportunities for viral vector engineering to test the hypothesis that combining genetic elements for viral payload expression (e.g., promoters and enhancers) with receptor- mediated virus binding will result in synergy to more specifically target desirable cell populations of interest to addiction researchers. Summary. Tools generated by the VIC will meet the needs of Center Investigators and Affiliates as they pursue their innovative research projects and will promote engagement with the other Research Cores. Furthermore, new multi-modal AAV targeting paradigms will benefit internal and external investigators who strive for more refined targeting of cells and circuits relevant to substance use disorders.