Of the approved RNA therapeutics, only ASOs have m 5 C and m 5 U. The ASOs have either a PMO backbone, a phosphorothioate backbone where all the nucleotides contain 2'-MOE groups, or a phosphorothioate backbone with blocks of nucleotides at the 5' and 3' ends containing 2'-MOE groups and internal 2'-deoxyribonucleotide residues. While the 2'-MOE groups protect the ASO from degradation, they also prevent RNase H digestion of the target mRNA. Thus, an ASO with an internal gap between the protected ends permits RNase H recognition of the target, which is the case for three of the four ASOs with 2'-MOE groups (Table ). ASOs with PMO backbones (see Figure ) regulate their targets through steric hindrance, not nuclease digestion. For the seven ASOs in Table , five have phosphorothioate backbones and two, Exondys 51 and Vyondys 53, have PMO backbones together with a triethylene glycol extension at their 5' end (Figure ).