Published on March 17, 2017 in Nucleic Acids Res volume 45(5).
PubMed ID: 27907896
Site-directed A-to-I RNA editing is a technology for re-programming geneticinformation at the RNA-level. We describe here the first design of geneticallyencodable guideRNAs that enable the re-addressing of human ADAR2 toward specificsites in user-defined mRNA targets. Up to 65% editing yield has been achieved incell culture for the recoding of a premature Stop codon (UAG) into tryptophan (UIG).In the targeted gene, editing was very specific. We applied the technology to recodea recessive loss-of-function mutation in PINK1 (W437X) in HeLa cells and showedfunctional rescue of PINK1/Parkin-mediated mitophagy, which is linked to theetiology of Parkinson's disease. In contrast to other editing strategies, thisapproach requires no artificial protein. Our novel guideRNAs may allow for thedevelopment of a platform technology that requires only the administration orexpression of a guideRNA to recode genetic information, with high potential forapplication in biology and medicine.CI - © The Author(s) 2016. Published by Oxford University Press on behalf of NucleicAcids Research.