Efficient and precise editing of endogenous transcripts with SNAP-tagged ADARs

Molecular tools that target RNA at specific sites allow recoding of RNA information and processing. SNAP-tagged deaminases guided by a chemically stabilized guide RNA can edit targeted adenosine to inosine in several endogenous transcripts simultaneously, with high efficiency (up to 90%), high potency, sufficient editing duration, and high precision. We used adenosine deaminases acting on RNA (ADARs) fused to SNAP-tag for the efficient and concurrent editing of two disease-relevant signaling transcripts, KRAS and STAT1 . We also demonstrate improved performance compared with that of the recently described Cas13b–ADAR. Fusion of a guide RNA directly to an adenosine deaminase via a SNAP-tag allows for precise and efficient RNA editing.