Leveraging Small Molecule-Induced Aptazyme Cleavage for Directed A-to-I RNA Editing

As a promising therapeutic approach for the correctionof pathogenicmutations, the RNA editing process is reversible and tunable withoutpermanently altering the genome. RNA editing mediated by human ADARproteins offers distinct advantages, including high specificity andlow propensity to cause immunogenicity. Herein, we describe a smallmolecule-inducible RNA editing strategy by incorporating aptazymesinto the guide RNA of ADAR-based RNA editing technology. Once smallmolecules are added or removed, aptazymes trigger self-cleavage torelease the guide RNA, achieving small molecule-controlled RNA editing.To satisfy different RNA editing applications, both turn-on and turn-offA-to-I RNA editing of target mRNA have been realized by using on/off-switchaptazymes. Theoretically speaking, this strategy can be applied tovarious ADAR-based editing systems, which could improve the safetyand potential clinical applications of RNA editing technology.