Precise in vivo RNA base editing with a wobble-enhanced circular CLUSTER guide RNA
Technology tamfitronics MainSite-directed adenosine-to-inosine (A-to-I) RNA base editing is a very promising technology with a clear path for clinical application1,2. Hydrolytic deamination of A by enzymes of the ADAR family (adenosine deaminases acting on RNA) produces an inosine, which is biochemically interpreted as G in many cellular processes such as splicing or translation and, consequently, functionally substitutes A with G on the RNA level3,4. There are three catalytically active human ADAR proteins: constitutively and ubiquitously expressed ADAR1 p110, interferon-inducible ADAR1 p150 and ADAR2. In the past, ADAR deaminase domains have been engineered into various artificial editing approaches that enable the efficient and highly programmable editing of any given target A in the transcriptome by applying...
