Chemically modified antisense oligonucleotides (asos) and compositions for rna editing

Abstract

The present disclosure relates to a chemically modified oligonucleotide for use in site-directed A-to-I editing of a target RNA inside a cell with endogenous adenosine deaminase acting on RNA (ADAR), the oligonucleotide comprising a sequence capable of binding to a target sequence in a target RNA and a central base triplet (CBT) of 3 nucleotides (5′-N+1 N0 N−1-3′), wherein N0 is the central nucleotide directly opposite to a target adenosine in the target RNA that is to be edited, and wherein the oligonucleotide comprises an asymmetry of 25-1-8 in a 5′ to 3′ direction; and comprises: (i) one or more phosphorothioate (PS) linkages at one or more of position +22, position +21, position +11, and position +4; and/or (ii) a 2′-O-methyl (2′-O-Me) modified nucleosides at position +13 and/or position +9.

Dependencies are inferred from the claim text.