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

Young, Adam; Neumann, Bjoern; Segel, Michael; Chen, Civia Zi-Yu; Tourlomousis, Panagiotis; Franklin, Robin J M · Proc Natl Acad Sci U S A · 2023

basic_science · Level V

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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.

Medical subject headings