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. 2022 Oct 9;12(16):7132–7157. doi: 10.7150/thno.77830

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Chemical modifications used in ASO and other OGT agents. A) Natural deoxynucleotides and ribonucleotides. B) First generation phosphorothioate (PS) modified nucleotide (sulfur-substituted for a non-bridging oxygen of the phosphate group). C) Second generation 2'-O-Methyl (2'-OMe) and 2'-O-Methoxyethyl (2'-MOE) modified nucleotides (2'-hydroxyl group of RNA substituted with 2'-OMe or 2'-MOE). D) Third generation phosphorodiamidate morpholino (PMO), peptide nucleic acid (PNA), locked nucleic acid (LNA) and constrained ethyl (cEt) with various sugar and phosphate modifications. E) Gapmer antisense oligonucleotides, consisting of a DNA-based internal 'gap' and RNA-modified flanking regions (the most common are 2ʹ-OMe and LNA). F) Novel amido-bridged nucleic acid (AmNA), 4'-C-OMe-2'-F-arabinonucleotide (araN) and 2'3'-dideoxy-2′-fluoro-3′-C-hydroxymethyl-β-D-lyxonucleotide modifications (see 2.2.2 for details).