Images of adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain

Output Details

Dataset of images supporting the publication: Chuapoco, M.R., Flytzanis, N.C., Goeden, N. et al. Adeno-associated viral vectors for functional intravenous gene transfer throughout the non-human primate brain. Nat. Nanotechnol. (2023). https://doi.org/10.1038/s41565-023-01419-x Publication 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.
Identifier (DOI)
10.35077/g.948
Tags
  • AAV (Adenoassociated Virus)
  • Central Nervous System (CNS)
  • Microscopy - optical
  • NHP (Non-Human Primate)
  • Non-human primate