Mapping the Structural Determinants Required for AAVrh.10 Transport across the Blood-Brain Barrier.

ABSTRACT: Effective gene delivery to the CNS by intravenously administered adeno-associated virus (AAV) vectors requires crossing the blood-brain barrier (BBB). To achieve therapeutic CNS transgene expression, high systemic vector doses are often required, which poses challenges such as scale-up costs and dose-dependent hepatotoxicity. To improve the specificity and efficiency of CNS gene transfer, a better understanding of the structural features that enable AAV transit across the BBB is needed. We generated a combinatorial domain swap library using AAV1, a serotype that does not traverse the vasculature, and AAVrh.10, which crosses the BBB in mice. We then screened individual variants by phylogenetic and structural analyses and subsequently conducted systemic characterization in mice. Using this a

SUBMITTER: Albright BH 

PROVIDER: S-EPMC5835146 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature