Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain
[ DOI: https://doi.org/10.35077/g.948 ]
Dataset Citation:
Gradinaru, Viviana. (2023). Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain. [ Collection / Dataset ]. Brain Image Library. https://doi.org/10.35077/g.948
Abstract:
Crossing the blood-brain-barrier in non-human primates (NHPs) is a major obstacle for gene delivery to the brain. Adeno-associated viruses (AAVs) promise robust gene delivery to the brain through non-invasive, intravenous delivery. However, unlike in rodents, few neurotropic AAVs efficiently cross the blood-brain barrier in non-human primates. Here, we report on AAV.CAP-Mac, an engineered variant identified by screening in adult marmosets and new-born macaques which has improved delivery efficiency in the brains of multiple NHP species: marmoset, rhesus macaque, and green monkey. CAP-Mac is neuron-biased in infant Old-World primates, exhibits broad tropism in adult rhesus macaques, and is vasculature-biased in adult marmosets. We demonstrate applications of a single, intravenous dose of CAP-Mac to deliver functional GCaMP for ex vivo calcium imaging across multiple brain areas, or a cocktail of fluorescent reporters for Brainbow-like labeling throughout the macaque brain, circumventing the need for germline manipulations in Old World primates. As such, CAP-Mac is shown to have potential for non-invasive systemic gene transfer in the brains of NHPs.
Funding:
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 1-UF1-MH128336-01 Engineered AAV Identification, Validation, and Dissemination Pipeline for Brain Cell Type-Specific Manipulation Across Species;
National Institutes of Health 5-P51-OD01107-61 California National Primate Research Center;
National Institutes of Health 5-R01-HD091325-05 Differentiation and Integration of Trisomy 21 iPSCs in an Animal Model;
National Institutes of Health 5-U19-NS123719-02 Astrocyte Modulation of Neural Circuit Function and Behavior;
National Institutes of Health 5-UG3-MH120095-03 Cell type selective viral tools to interrogate and correct non-human primate and human brain circuitry;
Aligning Science Across Parkinson's ASAP-020495 Gut-to-Brain Circuit Contributions to Parkinson-Like Phenotypes in Disease Models
Contributors:
Gradinaru, Viviana (ProjectLeader) [ORCID: https://orcid.org/0000-0001-5868-348X ] California Institute of Technology
Related Identifiers:
Requires [ URL : https://download.brainimagelibrary.org/79/db/79db776f5aca8090 ];Requires [ URL : https://download.brainimagelibrary.org/a9/d4/a9d4b1aa3c8e7c98 ];
Requires [ URL : https://download.brainimagelibrary.org/2d/64/2d646336e852f0c7 ];
Requires [ URL : https://download.brainimagelibrary.org/23/59/23593944f982feb6 ];
Requires [ URL : https://download.brainimagelibrary.org/37/e4/37e49bc0622a8c55 ];
Requires [ URL : https://download.brainimagelibrary.org/00/4e/004e8c8a93c64da8 ];
Requires [ URL : https://download.brainimagelibrary.org/51/e6/51e6cbb5cba54a7f ];
Requires [ URL : https://download.brainimagelibrary.org/d7/98/d7989982b6fed277 ];
Requires [ URL : https://download.brainimagelibrary.org/2a/c8/2ac8840607058f4b ];
Requires [ URL : https://download.brainimagelibrary.org/13/91/139156a2b5d829b0 ];
Requires [ URL : https://download.brainimagelibrary.org/4b/b2/4bb20321f3cdf762 ];
Requires [ URL : https://download.brainimagelibrary.org/a2/4f/a24fc9dc81be1333 ];
Requires [ URL : https://download.brainimagelibrary.org/eb/df/ebdfefe81ec2d012 ];
Requires [ URL : https://download.brainimagelibrary.org/dc/5d/dc5da4a8bda0d807 ];
Requires [ URL : https://download.brainimagelibrary.org/20/19/2019e3db9bd71c1e ];
Requires [ URL : https://download.brainimagelibrary.org/eb/a9/eba9d5034bfd6162 ];
Requires [ URL : https://download.brainimagelibrary.org/5d/7b/5d7b0d22b0604dd9 ];