In vivo RNA editing of point mutations via RNA-guided adenosine deaminases

Abstract

We utilized a system for sequence-specific RNA base editing via Adenosine Deaminases acting on RNA (ADAR) enzymes with associated ADAR guide RNAs (adRNAs). We systematically engineered it to harness ADARs, and comprehensively evaluated its specificity and activity in vitro and in vivo via two mouse models of human disease. We anticipate this platform will enable tunable and reversible engineering of RNAs for diverse applications.