From: Modified nucleic acids: replication, evolution, and next-generation therapeutics
Drug name (trade name) | Target | Modifications | Mechanism | Indication | Approval | Ref. |
---|---|---|---|---|---|---|
Fomivirsen (Vitravene) | mRNA of the CMV immediate-early (IE)-2 protein | PS | ASO (translation blocking) | Cytomegalovirus retinitis (CMV) | FDA (1998) and EMA (1999) approved. FDA (2001) and EMA (2002) withdrawn | [174] |
Pegaptanib (Macugen) | Vascular endothelial growth factor (VEGF165) | 2′F, 2′OMe, PEG conjugate | Aptamer | Neovascular (wet) age-related macular degeneration | FDA approved (2004) | [175] |
Mipomersen (Kynamro) | Apolipoprotein B-100 mRNA | 2′MOE, PS, 5mC | ASO (RNase H) | Homozygous familial hypercholesterolemia | FDA approved (2013) | [176] |
Eteplirsen (Exondys 51) | Exon 51 in dystrophin mRNA | PMO | ASO (splicing modulation) | Duchenne muscular dystrophy | FDA approved (2016) | [177] |
Nusinersen (Spinraza) | Survival of motor neuron 2 (SMN2) pre-mRNA | 2′MOE, PS, 5mC | ASO (splicing modulation) | Spinal muscular atrophy | FDA (2016) and EMA (2017) approved | [178] |
Patisiran (Onpattro) | Transthyretin (TTR) mRNA | 2′OMe | siRNA | Hereditary transthyretin-mediated amyloidosis | FDA and EMA approved (2018) | [179] |
Inotersen (Tegsedi) | Transthyretin (TTR) mRNA | 2′MOE, PS, 5mC | ASO (RNase H) | Hereditary transthyretin-mediated amyloidosis | FDA and EMA approved (2018) | [180] |
Volanesorsen (Waylivra) | Apolipoprotein C3 (apo-CIII) mRNA | 2′MOE, PS, 5mC | ASO (RNase H) | Familial chylomicronemia syndrome | EMA approved (2019) | [181] |
Givosiran (Givlaari) | Aminolevulinate synthase 1 (ALAS1) mRNA | PS, 2′F, 2′OMe, GalNAc conjugate | siRNA | Acute hepatic porphyria | FDA approved (2019) | [182] |
Golodirsen (Vyondys 53) | Exon 53 in dystrophin mRNA | PMO | ASO (splicing modulation) | Duchenne muscular dystrophy | FDA approved (2019) |