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

We present in vivo sequence-specific RNA base editing via adenosine deaminases acting on RNA (ADAR) enzymes with associated ADAR guide RNAs (adRNAs). To achieve this, we systematically engineered adRNAs to harness ADARs, and comprehensively evaluated the specificity and activity of the toolsets in vitro and in vivo via two mouse models of human disease. We anticipate that this platform will enable tunable and reversible engineering of cellular RNAs for diverse applications. RNA-guided adenosine deaminases edit point mutations in in vivo mouse models for Duchenne muscular dystrophy and ornithine transcarbamylase deficiency.