A high-efficiency AAV for endothelial cell transduction throughout the central nervous system

Endothelial cells have a crucial role in nervous system function and mounting evidence points to endothelial impairment as a major contributor to a wide range of neurological diseases; however, tools to genetically interrogate these cells in vivo remain limited. Here, we describe AAV-BI30, a capsid that specifically and efficiently transduces endothelial cells throughout the central nervous system. At relatively low systemic doses, this vector transduces the majority of arterial, capillary and venous endothelial cells in the brain, retina and spinal cord vasculature of adult C57BL/6 mice. Furthermore, we show that AAV-BI30 robustly transduces endothelial cells in multiple mouse strains and rats in vivo and human brain microvascular endothelial cells in vitro. Finally, we demonstrate the capacity of AAV-BI30 to achieve efficient and endothelial-specific Cre-mediated gene manipulation in the central nervous system. This combination of attributes makes AAV-BI30 well suited to address outstanding research questions in neurovascular biology and aid the development of therapeutics to remediate endothelial dysfunction in disease. Despite an emerging role for cerebrovascular endothelial cells in a range of neurological pathologies, AAV vector development to date has focused on tools designed to target neurons or astrocytes. Here, Krolak et al. describe a specific variant of AAV (AAV-BI30), with high specificity and efficacy for transduction of endothelial cells across the central nervous system.