CAG-Cre AAV (Serotype AAV-BI30)

While the degree of tropism for tissue types may vary between serotypes, the transduction spectrum of AAV is quite broad, with no clear specificity for tissue/cell types and overlap in tropism between different serotypes. Despite the lack of specificity and off-target tissue transduction, native AAV serotypes have been used in many clinical studies. In addition, different engineering strategies have been employed, resulting in novel AAV capsid variants that are highly enriched in multiple tissues via intravascular administration.

Recently, the use of the AAV9-CMV-Express platform, which relies on the recovery of library transcripts to ensure selection of transcriptionally functional variants, led to the identification of an AAV9-derived variant, AAV-BI30. This variant exhibited overall higher, broader, more selective, and strain-compatible endothelial cell transduction in vitro and in vivo compared to previously identified variants such as AAV-BR1. Following intravenous injection, AAV-BI30 targeted 84% of endothelial cells within the mouse central nervous system, reaching arteries, veins, and capillaries, as well as endothelial cells from peripheral organs such as the eye (69-81%), spinal cord (76%), lung, heart, and kidney. AAV-BI30 was more specific for brain endothelial cells in the central nervous system than AAV-PHP.V1, although it also demonstrated robust transduction of the liver. Importantly, AAV-BI30 exhibited similar transduction properties for brain endothelial cells from mice and rats, and was more efficient than AAV9 in transducing immortalized human brain microvascular endothelial cells (hCMEC/D3) as well as human and mouse brain microvascular endothelial cells (BMVEC) in vitro, suggesting potential for translational applicability.