Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California, USA; email:
Sainsbury Wellcome Centre, University College London, London, United Kingdom.
Annu Rev Neurosci. 2022 Jul 8;45:447-469. doi: 10.1146/annurev-neuro-111020-100834. Epub 2022 Apr 19.
Recombinant adeno-associated viruses (AAVs) are commonly used gene delivery vehicles for neuroscience research. They have two engineerable features: the capsid (outer protein shell) and cargo (encapsulated genome). These features can be modified to enhance cell type or tissue tropism and control transgene expression, respectively. Several engineered AAV capsids with unique tropisms have been identified, including variants with enhanced central nervous system transduction, cell type specificity, and retrograde transport in neurons. Pairing these AAVs with modern gene regulatory elements and state-of-the-art reporter, sensor, and effector cargo enables highly specific transgene expression for anatomical and functional analyses of brain cells and circuits. Here, we discuss recent advances that provide a comprehensive (capsid and cargo) AAV toolkit for genetic access to molecularly defined brain cell types.
重组腺相关病毒（AAV）是神经科学研究中常用的基因传递载体。它们具有两个可工程化的特征：衣壳（外壳蛋白）和货物（包裹的基因组）。这些特征可以被修饰以分别增强细胞类型或组织嗜性和控制转基因表达。已经鉴定出几种具有独特嗜性的工程化 AAV 衣壳，包括在中枢神经系统中具有增强转导能力、细胞类型特异性和神经元逆行运输的变体。将这些 AAV 与现代基因调控元件和最先进的报告基因、传感器和效应物货物结合使用，可以实现对脑细胞和回路进行解剖学和功能分析的高度特异性转基因表达。在这里，我们讨论了最近的进展，这些进展为基因进入分子定义的脑细胞类型提供了一个全面的（衣壳和货物）AAV 工具包。
