Gene

Point mutation

Cell biology

Biology

ADAR

Adenosine deaminase

Genome editing

CRISPR

Mutation

Biochemistry

Computational biology

Genetics

In vivo

RNA editing

Adenosine

Nucleic acid structure

Non-coding RNA

Guide RNA

Nature Methods

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.

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