Selection of rAAV vectors that cross the human blood-brain barrier and target the central nervous system using a transwell model.

ABSTRACT: A limitation for recombinant adeno-associated virus (rAAV)-mediated gene transfer into the central nervous system (CNS) is the low penetration of vectors across the human blood-brain barrier (BBB). High doses of intravenously delivered vector are required to reach the CNS, which has resulted in varying adverse effects. Moreover, selective transduction of various cell types might be important depending on the disorder being treated. To enhance BBB penetration and improve CNS cell selectivity, we screened an AAV capsid-shuffled library using an in vitro transwell BBB system with separate layers of human endothelial cells, primary astrocytes and/or human induced pluripotent stem cell-derived cortical neurons. After multiple passages through the transwell, we identified chimeric AAV cap

SUBMITTER: Song R 

PROVIDER: S-EPMC9494039 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature