Efficient in vitro and in vivo RNA editing via recruitment of endogenous ADARs using circular guide RNAs.

ABSTRACT: Recruiting endogenous adenosine deaminases using exogenous guide RNAs to edit cellular RNAs is a promising therapeutic strategy, but editing efficiency and durability remain low using current guide RNA designs. In this study, we engineered circular ADAR-recruiting guide RNAs (cadRNAs) to enable more efficient programmable adenosine-to-inosine RNA editing without requiring co-delivery of any exogenous proteins. Using these cadRNAs, we observed robust and durable RNA editing across multiple sites and cell lines, in both untranslated and coding regions of RNAs, and high transcriptome-wide specificity. Additionally, we increased transcript-level specificity for the target adenosine by incorporating interspersed loops in the antisense domains, reducing bystander editing. In vivo delivery of cad

SUBMITTER: Katrekar D 

PROVIDER: S-EPMC9232839 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature