In a recent publication in Cell Chemical Biology (Monteleone and coworkers, A Bump-Hole Approach for Directed RNA Editing, 2018) the Beal and Fisher labs describe a site directed-RNA editing system with reduced off-target activity. A variety of systems have been developed to direct reactions that change nucleic acid sequences, either in DNA (genome editing) or in RNA (transcriptome editing) and these systems are transforming molecular biology and medicine. However, it is essential that such tools be highly precise as unwanted changes in nucleic acid sequences can be lethal. The bump-hole strategy described in this paper uses bulky mutations to the catalytic site of an RNA editing adenosine deaminase (ADAR2) in combination with chemically modified guide RNAs (see below). Efficient directed RNA editing was demonstrated in vitro and in human cells with reduced off-target activity.
More information at https://www.ncbi.nlm.nih.gov/pubmed/30581135