Department of Clinical Neurosciences, Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, United Kingdom.
Department of Clinical Neurosciences, Altos Labs-Cambridge Institute of Sciences, Cambridge CB21 6GP, United Kingdom.
Proc Natl Acad Sci U S A. 2023 Aug 29;120(35):e2302997120. doi: 10.1073/pnas.2302997120. Epub 2023 Aug 21.
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.
组织巨噬细胞,包括小神经胶质细胞,是出了名的难以进行基因操作。在这里,我们报告了腺相关病毒(AAV)变体的创建,这些变体在静脉注射后能够有效地广泛转导体内的小神经胶质细胞和组织巨噬细胞,转导基因的表达高达 80%。我们使用这项技术来演示对小神经胶质细胞基因表达的操作和小神经胶质细胞的清除,从而为这些重要细胞的研究提供了非常有价值的研究工具。