AAV-CRISPR-Cas13 eliminates human enterovirus and prevents death of infected mice.

ABSTRACT:

Background

RNA viruses account for many human diseases and pandemic events but are often not targetable by traditional therapeutics modalities. Here, we demonstrate that adeno-associated virus (AAV) -delivered CRISPR-Cas13 directly targets and eliminates the positive-strand EV-A71 RNA virus in cells and infected mice.

Methods

We developed a Cas13gRNAtor bioinformatics pipeline to design CRISPR guide RNAs (gRNAs) that cleave conserved viral sequences across the virus phylogeny and developed an AAV-CRISPR-Cas13 therapeutics using in vitro viral plaque assay and in vivo EV-A71 lethally-infected mouse model.

Findings

We show that treatment with a pool of AAV-CRISPR-Cas13-gRNAs designed using the bioinformatics pipeline effectively blocks viral replication and reduces vira

SUBMITTER: Keng CT 

PROVIDER: S-EPMC10363442 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature