Table 1:
Current FDA-approved RNA therapeutics.
| Therapeutics | Approval year | Disease (cellular target) | Type | Mechanism of action | Key modifications | Delivery strategy |
|---|---|---|---|---|---|---|
| Formivirsen | 1998 | CMV retinitis | ASO | RNA degradation | PS | Intravitreal |
| Pegaptanib | 2004 | Macular degeneration (VEGF) | Aptamer | VEGF antagonist | 2′-OMe, 2′-F | Intravitreal, PEG conjugated |
| Mipomersen | 2013 | Familial hypercholesterolemia (ApoB) | ASO | RNA degradation | 2′-MOE, PS | Subcutaneous |
| Nusinersen | 2016 | Spinal muscular atrophy (SMN2) | ASO | Splice switching | 2′-MOE, PS | Intrathecal |
| Eteplirsen | 2016 | DMD (dystrophin exon 51) | ASO | Splice switching | PMO | Intravenous infusion |
| Patisiran | 2018 | hATTR amyloidosis (TTR) | siRNA | RNA degradation | 2′-OMe, dT | Intravenous, LNP packaged |
| Inotersen | 2018 | hATTR amyloidosis (TTR) | ASO | RNA degradation | 2′-MOE | Subcutaneous |
| Milasen | 2018 | Ceroid lipofuscinosis 7 (MFSD8) | ASO | Splice switching | PS, 2′-OMe | Intrathecal |
| Givosiran | 2019 | Acute hepatic porphyria (aminolevulinate synthase) | siRNA | RNA degradation | 2′-OMe, 2′-deoxy-2′-F, PS | Subcutaneous, GalNAc conjugated |
| Golodirsen | 2019 | DMD (dystrophin exon 53) | ASO | Splice switching | PMO | Intravenous infusion |
| Lumasiran | 2020 | Primary hyperoxaluria type 1 (HAO1) | siRNA | RNA degradation | 2′-OMe, 2′-deoxy-2′-F, PS | Subcutaneous, GalNAc conjugated |
| Inclisiran | 2020 | Hypercholesterolemia (PCSK9) | siRNA | RNA degradation | 2′-OMe, 2′-deoxy-2′-F, PS | Subcutaneous, GalNAc conjugated |
| Viltolarsen | 2020 | DMD (dystrophin exon 53) | ASO | Splice switching | PMO | Intravenous infusion |
| Risdiplam | 2020 | Spinal muscular atrophy (SMN2) | Small molecule | Splice switching | NA | Oral |
| BNT162b2 | 2020 | COVID | mRNA | Antigen expression | m1Ψ | Intramuscular, LNP packaged |
| mRNA-1273 | 2020 | COVID | mRNA | Antigen expression | m1Ψ | Intramuscular, LNP packaged |
| Casimersen | 2021 | DMD (dystrophin exon 45) | ASO | Splice switching | PMO | Intravenous infusion |
| Vutrisiran | 2022 | hATTR amyloidosis (TTR) | siRNA | RNA degradation | 2′-OMe, 2′-deoxy-2′-F, PS | Subcutaneous, GalNAc conjugated |
| Avacincaptad pegol | 2023 | Geographic atrophy (C5) | Aptamer | C5 antagonist | 2′-F, 2′-OMe | Intravitreal, PEG conjugated |
| Tofersen | 2023 | Amyotrophic lateral sclerosis (SOD1) | ASO | RNA degradation | 2′-MOE, PS | Intrathecal |
| Nedosiran | 2023 | Primary hyperoxaluria type 1 (LDH) | siRNA | RNA degradation | 2′-Deoxy-2′-F, 2′-OMe, PS | Subcutaneous, GalNAc conjugated |
| Eplontersen | 2023 | hATTR amyloidosis (TTR) | ASO | RNA degradation | 2′-MOE, PS | Subcutaneous, GalNAc conjugated |
Note: CMV, cytomegalovirus; PEG, polyethylene glycol; VEGF, vascular endothelial growth factor; 2′-OMe, 2′-O-methyl; 2′-F, 2′-fluoro; 2′-MOE, 2′-methoxyethyl; PS, phosphorothioate; hATTR, hereditary transthyretin-mediated; LNP, lipid nanoparticle; PMO, phosphorodiamidate morpholino oligonucleotide; dT, 2′-deoxythymidine; DMD, Duchenne muscular dystrophy; m1Ψ, 1-methyl-3′-pseudouridylyl; LDH, lactate dehydrogenase; GalNAc, N-acetylgalactosamine; ApoB, apolipoprotein B; SMN2, survival motor neuron 2; MFSD8, major facilitator superfamily domain containing 8; HAO1, hydroxyacid oxidase 1; PCSK9, proprotein convertase subtilisin/kexin type 9; LDH, lactate dehydrogenase; SOD1, superoxide dismutase 1; NA, not applicable.