Adeno-Associated Virus Toolkit to Target Diverse Brain Cells

• Published in: Annual review of neuroscience Vol. 45; no. 1; pp. 447 - 469
• Main Authors: Challis, Rosemary C, Ravindra Kumar, Sripriya, Chen, Xinhong, Goertsen, David, Coughlin, Gerard M, Hori, Acacia M, Chuapoco, Miguel R, Otis, Thomas S, Miles, Timothy F, Gradinaru, Viviana
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 08.07.2022; Annual Reviews, Inc
• Subjects: AAV; adeno-associated virus; Axonal transport; Capsids; Central nervous system; Gene transfer; Genomes; Nervous system; Regulatory sequences; Retrograde transport; systemic delivery; targeted brain delivery; Tropism; viral capsid engineering; viral cargo
• ISSN: 0147-006X; 1545-4126
• DOI: 10.1146/annurev-neuro-111020-100834

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.