Blood-brain barrier-penetrant AAV vectors for cell type-specific gene expression in the mouse brain.

Since the report in 2016 of AAV-PHP.B, a capsid variant of adeno-associated virus (AAV) capable of efficiently penetrating the mouse blood-brain barrier (BBB), numerous other BBB-penetrant capsid variants have been developed. These variants differ in their use of membrane-bound receptors expressed on vascular endothelial cells, their BBB permeability, and their tropism toward specific brain cell types. In the first half of this paper, we provide an overview of four representative BBB-penetrant AAV capsid variants-PHP.B, PHP.eB, AAV-F, and 9P31. By combining these capsids with cell type-specific promoters, it is possible to achieve transgene expression selectively in target brain cell populations via intravenous administration. In the latter half of this paper, we focus on brain cell type-specific promoters and enhancers that are compatible with AAV packaging, including those developed in our own laboratory.