Abstract: The present invention relates to a chemically modified oligonucleotide for use in site-directed A-to-I editing of a target RNA inside a cell with endogenous ADAR, comprising a sequence with a length of 11 to 100 nucleotides capable of binding to a target sequence in the target RNA, with a Central Base Triplet of 3 nucleotides with the central nucleotide opposite to the target adenosine in the target RNA, which is to be edited to an inosine, whereby the core sequence has the following Formula I: wherein Nu stands for a nucleotide having a sugar moiety which may be modified, the numbers below the nucleotide sequence designate the position of the nucleotides adjacent to the central nucleotide of the Central Base Triplet having the number 0 whereby the negative numbers designate the 5? end and the positive number designate the 3? end of the oligonucleotide and wherein a-j designate the nature of the linkage between the single nucleotides whereby at least linkages a, d, and e are phosphorothioate linkages and

Abstract: The present invention concerns artificial nucleic acids for site-directed editing of a target RNA. In particular, the present invention provides artificial nucleic acids capable of site-directed editing of endogenous transcripts by harnessing an endogenous deaminase. Further, the present invention provides artificial nucleic acids for sited-directed editing of a target RNA, which are chemically modified, in particular according to a modification pattern as described herein. The invention also comprises a vector encoding said artificial nucleic acid and a composition comprising said artificial nucleic acid. Moreover, the invention provides the use of the artificial nucleic acid, the composition or the vector for site-directed editing of a target RNA or for in vitro diagnosis. In addition, the artificial nucleic acid, the composition or the vector as described herein are provided for use as a medicament or for use in diagnosis of a disease or disorder.

Abstract: The invention relates to methods and substances for the targeted alteration of genetic information on an RNA level. The substances are artificially produced guide RNAs, which are capable of recruiting endogenous editing enzymes, such as hADAR enzymes, in particular hADAR2 and hADAR1, in order to introduce targeted point mutations in selected mRNAs. The guide RNA consists of multiple segments and is constructed in such a way that individual nucleotides from different segments pair to form a double helix, and the nucleotides of a determined segment form a hairpin structure within the guide RNA. The invention also relates to the method for directed RNA editing, wherein the guide RNA is transfected into the cells in which the RNA editing is to be carried out. The substances and the method can be used for repairing individual, e.g. disease-relevant point mutations, such as those leading to premature stop signals.