biostudies-literatureUnknownChuapoco MRNIMH NIH HHSNIH HHSAdeno-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 fluorescResearch squarers.3.rs-1370972https://www.ebi.ac.uk/biostudies/studies/S-EPMC9928057biostudies-literatureIntravenous functional gene transfer throughout the brain of non-human primates using AAV.PMC9928057UF1 MH128336P51 OD011107Deverman BELefevre AFox ASMan KNMTaskin NOcteau JCCampos LJBishaw YWinchester JWeed NScherrer JMich JVendemiatti JGradinaru VArokiaraj CMBlackburn RJChuapoco MRChen XShaya TFPickel JChan KYSun JFlytzanis NCSingh VPTian LGore BOmstead VMiller CTTing JGoeden NRoxas KMJang MJfalseIntravenous functional gene transfer throughout the brain of non-human primates using AAV.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 fluoresc2023-01-01T00:00:00Z2023 Jan2026-06-04T03:10:01.193Z2025-04-04T13:07:29.351ZS-EPMC99280573678943210.21203/rs.3.rs-1370972/v1