Table 1.
Oligonucleotide Types and Their Exon Skipping, Exon Inclusion, and Related Applications
| Oligonucleotide* | Cellular target | ES | EI | Other | Therapeutic application | Reference |
|---|---|---|---|---|---|---|
| Negatively charged ON Analogues | ||||||
| DNA-PS | pre-mRNA | x | DMD | Takeshima et al., 2006 | ||
| OMe | pre-mRNA | x | DMD | Fletcher et al., 2006; Lu et al., 2005; | ||
| x | Goemans et al., 2011; | |||||
| pre-mRNA | x | Dystrophic epidermolysis Bullosa | Goto et al., 2006 | |||
| DMPK-mRNA | x | Myotonic dystrophy type 1 | González-Barrigs et al., 2013; Mulders et al., 2009 | |||
| pre-mRNA | x | Lowering LDL cholesterol | Disterer et al., 2013 | |||
| pre-mRNA | x | SMA | Osman et al., 2012 | |||
| MOE | pre-mRNA | x | SMA | Hua et al., 2010; Passini et al., 2011 | ||
| MOE gapmers | DMPK-mRNA | x | Myotonic dystrophy type 1 | Wheeler et al., 2012 | ||
| LNA | pre-mRNA | x | DMD | Aartsma-Rus et al., 2004 | ||
| pre-mRNA | x | Rheumatoid arthritis | Graziewicz et al., 2008 | |||
| pre-mRNA | x | Chronic inflammatory disease | Yilmaz-Elis et al., 2013 | |||
| TcDNA | pre mRNA | x | DMD | Goyenvalle et al., 2013 | ||
| MCE | pre mRNA | x | DMD | Yamada et al., 2011 | ||
| Charge-neutral ON analogues | ||||||
| PNA | pre-mRNA | x | DMD | Yin et al., 2008a; Yin et al., 2010 | ||
| PMO | pre-mRNA | x | DMD | For reviews see Moulton and Moulton, 2008; | ||
| x | Moulton and Moulton, 2010 | |||||
| pre-mRNA | x | SMA | Porensky et al., 2012; Zhou et al., 2013 | |||
| DMPK-mRNA | x | Myotonic dystrophy type 1 | Wheeler et al., 2009; Koebis et al., 2013 | |||
| Peptide or polymer ON delivery | ||||||
| PEG-PEI with OMe-PS ONs | pre-mRNA | x | DMD | Sirsi et al., 2008; Ferlini et al., 2010; | ||
| x | Bassi et al., 2012 | |||||
| PEG-PEI with PMO | pre-mRNA | x | DMD | Wang et al., 2013 | ||
| Pip2b-PNA | pre-mRNA | x | DMD | Ivanova et al., 2008 | ||
| B/R-peptide-PMO | pre-mRNA | x | DMD | Jearawiriyapaisarn et al., 2008; Wu et al., 2008; | ||
| x | Yin et al., 2008b; Wu et al., 2012 | |||||
| DMPK-mRNA | x | Myotonic dystrophy type 1 | Leger et al., 2013 | |||
| Pip5-PMO, Pip6-PMO | pre-mRNA | x | DMD | Yin et al., 2011; Betts et al., 2012 | ||
| Vivo-morpholinos | pre-mRNA | x | DMD | Wu et al., 2009; Widrick et al., 2011; Yokota et al., 2012; Aoki et al., 2012 | ||
*
For chemical structures of oligonucleotide (ON) types, see Fig. 1.
DMD, Duchenne muscular dystrophy; DMPK, dystrophia myotonica protein kinase; EI, exon inclusion; ES, exon skipping; LDL, low-density lipoprotein; LNA, locked nucleic acid; MCE, 2′-O-[2-(N-methylcarbamoyl)ethyl]uridine; MOE, 2′-O-methoxyethyl; OMe, 2′-O-methyl; PEG–PEI, polyethylene glycol–poly(ethylene imine); Pip, PMO internalization peptides; PMO, phosphorodiamidate morpholino; PNA, peptide nucleic acids; PS, phosphorothioate; SMA, spinal muscular atrophy; TcDNA, tricycloDNA.