| Title: |
Intravenous functional gene transfer throughout the brain of non-human primates using AAV |
| Authors: |
Chuapoco, Miguel; Flytzanis, Nicholas; Goeden, Nick; Octeau, J; Roxas, Kristina; Chan, Ken; Scherrer, Jon; Winchester, Janet; Blackburn, Roy; Campos, Lillian; Man, Kwun-Nok; Sun, Junqing; Chen, Xinhong; Lefevre, Arthur; Singh, Vikram; Arokiaraj, Cynthia; Miles, Timothy; Vendemiatti, Julia; Jang, Min; Mich, John; Bishaw, Yeme; Gore, Bryan; Omstead, Victora; Taskin, Naz; Weed, Natalie; Ting, Jonathan; Miller, Cory; Deverman, Benjamin; Pickel, James; Tian, Lin; Fox, Andrew; Gradinaru, Viviana |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2023 |
| Description: |
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 (NHPs). Here we describe AAV.CAP-Mac, an engineered variant identified by screening in adult marmosets and newborn macaques with improved efficiency in the brain 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 (1) functional GCaMP for ex vivo calcium imaging across multiple brain areas, and (2) a cocktail of fluorescent reporters for Brainbow-like labeling throughout the macaque brain, circumventing the need for germline manipulations in Old World primates. Given its capabilities for systemic gene transfer in NHPs, CAP-Mac promises to help unlock non-invasive access to the brain. |
| Document Type: |
other/unknown material |
| Language: |
unknown |
| DOI: |
10.21203/rs.3.rs-1370972/v1 |
| Availability: |
https://doi.org/10.21203/rs.3.rs-1370972/v1; https://www.researchsquare.com/article/rs-1370972/v1; https://www.researchsquare.com/article/rs-1370972/v1.html |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.7E84B0A5 |
| Database: |
BASE |