Targeted evolution of adeno-associated virus capsids for systemic transgene delivery to microglia and tissue-resident macrophages
Adam M. H. Young, Bjoern Neumann, Michael Segel, Civia Z. Chen, Panagiotis Tourlomousis, Robin J.M. Franklin
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.
Topics & Concepts
MicrogliaTransgeneGene deliveryAdeno-associated virusBiologyCapsidGenetic enhancementIn vivoCell biologyGenetically modified mouseVirusVirologyGeneGeneticsImmunologyVector (molecular biology)Recombinant DNAInflammationVirus-based gene therapy researchRNA Interference and Gene DeliveryCRISPR and Genetic Engineering