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

Molecular tools to target RNA site-specifically allow recoding of RNA information and processing. SNAP-tagged deaminases, guided by a chemically stabilized guideRNA, enable the simultaneous editing of targeted adenosine to inosine in several endogenous transcripts, with high efficiency (up to 90%), high potency, sufficient duration, and high precision. We applied SNAP-ADARs for the efficient and concurrent editing of two disease-relevant signaling transcripts, KRAS and STAT1. We also show improved performance compared to the recently described Cas13b-ADAR. Overall design: Identification of off-target editing events in SNAP-ADAR cell lines by RNA-Seq, 7 samples, 2 biologically independent experiments