Research square · 2023
Intravenous functional gene transfer throughout the brain of non-human primates using AAV.
ПрепринтСтатьяНазвание и аннотация: Перевод в очереди
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Chuapoco Miguel R, Flytzanis Nicholas C, Goeden Nick, Octeau J Christopher, 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, Shaya Timothy F, Vendemiatti Julia, Jang Min J, Mich John, Bishaw Yeme, Gore Bryan, Omstead Victoria, Taskin Naz, Weed Natalie, Ting Jonathan, Miller Cory T, Deverman Benjamin E, Pickel James, Tian Lin, Fox Andrew S, Gradinaru Viviana
Аннотация
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.