Multiplexed Cre-dependent selection yields systemic AAVs for targeting distinct brain cell types.

ABSTRACT: Recombinant adeno-associated viruses (rAAVs) are efficient gene delivery vectors via intravenous delivery; however, natural serotypes display a finite set of tropisms. To expand their utility, we evolved AAV capsids to efficiently transduce specific cell types in adult mouse brains. Building upon our Cre-recombination-based AAV targeted evolution (CREATE) platform, we developed Multiplexed-CREATE (M-CREATE) to identify variants of interest in a given selection landscape through multiple positive and negative selection criteria. M-CREATE incorporates next-generation sequencing, synthetic library generation and a dedicated analysis pipeline. We have identified capsid variants that can transduce the central nervous system broadly, exhibit bias toward vascular cells and astrocytes, target neur

SUBMITTER: Ravindra Kumar S 

PROVIDER: S-EPMC7219404 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature