Confocal imaging of the AAV-X1 family of engineered viral vectors that target brain endothelial cells in rodents and the broader CNS in primates

[ DOI: https://doi.org/10.35077/g.1149 ]

 

Dataset Citation:

Gradinaru, Viviana, Gradinaru Lab. (2023). Confocal imaging of the AAV-X1 family of engineered viral vectors that target brain endothelial cells in rodents and the broader CNS in primates. [ Collection / Dataset ]. Brain Image Library. https://doi.org/10.35077/g.1149

 

Abstract:

This data collection contains images of brains of various species transduced with novel engineered viral vectors from the publication "Functional gene delivery to and across brain vasculature of systemic AAVs with endothelial-specific tropism in rodents and broad tropism in primates." We have evolved adeno-associated virus (AAV9) capsids into vectors that transduce brain endothelial cells specifically and efficiently following systemic administration in wild-type mice with diverse genetic backgrounds, and in rats. These AAVs also exhibit superior transduction of the CNS across non-human primates (marmosets and rhesus macaques), and in ex vivo human brain slices, although the endothelial tropism is not conserved across species. The capsid modifications translate from AAV9 to other serotypes such as AAV1 and AAV-DJ, enabling serotype switching for sequential AAV administration in mice. We demonstrate that the endothelial-specific mouse capsids can be used to genetically engineer the blood-brain barrier by transforming the mouse brain vasculature into a functional biofactory. We apply this approach to Hevin knockout mice, where AAV-X1-mediated ectopic expression of the synaptogenic protein Sparcl1/Hevin in brain endothelial cells rescued synaptic deficits.

 

Funding:

National Institutes of Health 3-DP2-NS087949-02 Neuromodulation and Neurodegeneration: the Missing Link and Mechanisms of Action;
National Institutes of Health 1-UF1-MH128336-01   Engineered AAV Identification, Validation, and Dissemination Pipeline for Brain Cell Type-Specific Manipulation Across Species;
National Institutes of Health 5-DP1-NS111369-04 Circuit-Specific Delivery of Large Cargo Across the Nervous Systems of Adult Mammals and Embryos via Novel Engineered Systemic Vectors;
National Institutes of Health 3-OT2-OD024899-01 Comprehensive Structural and Functional Mapping of Mammalian Colonic Nervous System;
The Vallee Foundation NA Crossing the Blood-Brain Barrier for Brain-Wide Anatomical and Functional Mapping of Glia with Novel AAVs and CLARITY;
Gordon and Betty Moore Foundation NA Inventor Fellow;
Chan Zuckerberg Initiative NA Non-Canonical Pathways Towards Rescue from Neurodegenerative States;
National Science Foundation 1707316.0 NeuroNex Technology Hub: Multimodal Integrated Neural Technologies (MINT) - Connecting Physiology to Functional Mapping;
California Institute of Technology NA Heritage Medical Research Institute Investigator Program;
California Institute of Technology NA Beckman Institute for CLARITY, Optogenetics and Vector Engineering Research (CLOVER);
National Institutes of Health 5-UG3-MH120095-03  Cell type selective viral tools to interrogate and correct non-human primate and human brain circuitry;
National Institutes of Health 2-P51-OD011107-62  California National Primate Research Center;
Swiss National Science Foundation 310030_188952 Role of microglia in small vessel calcification in brain;
Synapsis Foundation 2019-P102 Astrocyte development and function in primary familial brain calcification;
Schweizerische Multiple Sklerose Gesellschaft NA NA;
Howard Hughes Medical Institute NA Investigator Program

 

Contributors:

Gradinaru, Viviana (ProjectLeader) [ORCID: https://orcid.org/0000-0001-5868-348X ] California Institute of Technology
Gradinaru Lab (ResearchGroup) California Institute of Technology

 

Related Identifiers:

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