Publications
Nature nanotechnologyJul 2023 DOI:
10.1038/s41565-023-01419-x

Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain

Chuapoco, Miguel R; Flytzanis, Nicholas C; Goeden, Nick; Christopher Octeau, J; Roxas, Kristina M; Chan, Ken Y; Scherrer, Jon; Winchester, Janet; Blackburn, Roy J; Campos, Lillian J; Man, Kwun Nok Mimi; Sun, Junqing; Chen, Xinhong; Lefevre, Arthur; Singh, Vikram Pal; Arokiaraj, Cynthia M; Shay, Timothy F; Vendemiatti, Julia; Jang, Min J; Mich, John K; Bishaw, Yemeserach; Gore, Bryan B; Omstead, Victoria; Taskin, Naz; Weed, Natalie; Levi, Boaz P; Ting, Jonathan T; Miller, Cory T; Deverman, Benjamin E; Pickel, James; Tian, Lin; Fox, Andrew S; Gradinaru, Viviana
Product Used
Variant Libraries
Abstract
Crossing the blood-brain barrier in primates is a major obstacle for gene delivery to the brain. Adeno-associated viruses (AAVs) promise robust, non-invasive gene delivery from the bloodstream to the brain. 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 newborn macaques, which has improved delivery efficiency in the brains of multiple non-human primate 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 labelling 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 non-human primates.
Product Used
Variant Libraries

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