RNA therapeutics approved by the US Food and Drug Administration for the treatment of human diseases
Note that two PMO drugs are included because the nucleobase thymine (T) is also known as 5-methyluracil, or m5U.
| RNA Drug | Chemistry | Dosage Regimen | Mechanisms of Action | Disease | Year Approved | Current Status | References |
|---|---|---|---|---|---|---|---|
| Pegaptanib (aptamer) | 28-nt aptamer; pegylated, all PO, 2′-F, and 2′-OMe; G and A methylated; mol. wt. ∼50 kDa | 0.3 mg every 6 wk, intravitreal injection | Selective VEGF (165 isoform) antagonist; antiangiogenesis in the eye | Neovascular AMD | 2004 | Prescription | Gragoudas et al., 2004; Gryziewicz, 2005 |
| Mipomersen (ASO) | 20-mer gapmer; all PS, 2ʹ-MOE, and 2′-deoxy; C and U methylated; mol. wt. ∼7.6 kDa | 200 mg once weekly, s.c. | Selectively binds to ApoB-100 mRNA to inhibit the translation of synthesis of ApoB in liver | HoFH | 2013 | Discontinued in 2018 | Crooke and Geary, 2013; Morrow, 2013 |
| Eteplirsen (ASO) | 30-mer PMO; m5U; mol. wt. ∼10.3 kDa | 30 mg/kg once weekly, i.v. infusion | Selectively binds to exon 51 of dystrophin pre-mRNA to alter splicing, leading to production of functional muscle protein dystrophin | DMD | 2016 | Prescription | Cirak et al., 2011; Mendell et al., 2016; Stein, 2016; Syed, 2016 |
| Nusinersen (ASO) | 18-mer; all PS, fully 2ʹ-MOE; m5U; m5C; mol. wt. ∼7.5 kDa | Loading: 12 mg every 2 wk for three doses, then 12 mg for 30 days, i.t. Maintenance: 12 mg once every 4 mo, i.t. | Selectively binds to SMN2 mRNA to alter splicing, leading to the production of full-length SMN protein | SMA | 2016 | Prescription | Aartsma-Rus, 2017; Ottesen, 2017 |
| Patisiran (siRNA) | 21-bp double-stranded siRNA; all PO, and 2ʹ-OMe; lipid nanoparticle mol. wt. ∼14.3 kDa | 0.3 mg/kg (b.wt. < 100 kg) or 30 mg (b.wt. ≥ 100 kg), every 3 wk, i.v. infusion | Selectively binds to TTR mRNA to decrease hepatic production of TTR protein | hATTR amyloidosis | 2018 | Prescription | Adams et al., 2018; Wood, 2018; Zhang et al., 2020b |
| Inotersen (ASO) | 20-mer gapmer; all PS, 2ʹ-MOE, and 2′-deoxy; C and U methylated; mol. wt. ∼7.2 kDa | 284 mg once weekly, s.c. | Selectively binds to TTR mRNA to cause mRNA degradation and reduce protein production | hATTR amyloidosis | 2018 | Prescription | Benson et al., 2018; Keam, 2018 |
| Givosiran (siRNA) | Double-stranded siRNA; PO and PS, 2-F′, 2′-O-Me, and triantennary GalNAc; mol. wt. ∼16.3 kDa | 2.5 mg/kg once monthly, s.c. | Selectively binds to hepatic ALAS1 mRNA, leading to ALAS1 mRNA degradation through RNA interference | AHP | 2019 | Prescription | Sardh et al., 2019; de Paula Brandao et al., 2020; Scott, 2020 |
| Golodirsen | 25-mer PMO; m5U; mol. wt. ∼8.6 kDa | 30 mg/kg once weekly, i.v. infusion | Selectively binds to exon 53 of dystrophin pre-mRNA to alter splicing, leading to production of functional muscle protein dystrophin in patients with genetic mutations that are amenable to exon 53 skipping | DMD | 2019 | Prescription | Heo, 2020 |
2′-F, 2′-fluoro; 2′-OMe, 2′-methoxy.