Targeted evolution of adeno-associated virus capsids for systemic transgene delivery to microglia and tissue-resident macrophages

Proc Natl Acad Sci U S A. 2023 Aug 29;120(35):e2302997120. doi: 10.1073/pnas.2302997120. Epub 2023 Aug 21.

Abstract

Tissue macrophages, including microglia, are notoriously resistant to genetic manipulation. Here, we report the creation of Adeno-associated viruses (AAV) variants that efficiently and widely transduce microglia and tissue macrophages in vivo following intravenous delivery, with transgene expression of up to 80%. We use this technology to demonstrate manipulation of microglia gene expression and microglial ablation, thereby providing invaluable research tools for the study of these important cells.

Keywords: AAV; brain; gene therapy; microglia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capsid
  • Dependovirus* / genetics
  • Macrophages
  • Microglia*
  • Transgenes