NeuroD1 Regulated Endothelial Gene Expression to Modulate Transduction of AAV-PHP.eB and Recovery Progress after Ischemic Stroke.

ABSTRACT: AAV-PHP.eB depends on endothelial cells to highly transduce the central nervous system (CNS) and is widely used for intravenous gene therapy. However, the transduction profile and therapeutic efficiency after endothelial cell injury such as ischemic stroke is largely unknown. In this study, we tested the transduction profiles of AAV-PHP.eB and developed intravenous NeuroD1 gene therapy to treat ischemic stroke in mice. We found that AAV-PHP.eB-GFP control virus crossed the BBB and infected brain cells efficiently in normal brain. However, after stroke, AAV-PHP.eB-GFP control virus was highly restricted in the blood vessels. Surprisingly, after switching to therapeutic vector AAV-PHP.eB-NeuroD1-GFP, the viral vector successfully crossed blood vessels and infected brain cells. Using Tie2-cre

SUBMITTER: He X 

PROVIDER: S-EPMC11567258 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature