TABLE 1

Chemistries of individual FDA-approved RNAi therapeutics. Sense and antisense sequences were obtained from the FDA inserts. Interestingly, the sense strand of newly approved nedosiran is designed to form a hairpin or stem-loop structure in which the loop is comprised of four GalNAc aminosugar conjugated ribonucleosides. As another note, the guanosine at position 6 from the 5’ end of the nedosiran antisense strand is instead called a cytosine in an alternative source (Siramshetty et al., 2022) to the FDA label.

RNA TherapeuticChemistryYear approved
Patisiran (Onpattro)Sense: 5′-GUmAACmCmAAGAGUmAUmUmCmCmAUmdTdT-3′
Antisense: 3′-dTdTCAUmUGGUUCUCAUmAAGGUA-5′
2018
Givosiran (Givlaari)Sense: 5′-CmsAmsGmAmAmAmGfAmGfUmGfUmCfUmCfAmUmCmUmUmAm-L96-3′
Antisense: 3′-UmsGmsGmUfCmUfUmUfCmUfCmAfCmAfGmAfGmUfAmGfAfsAfsUm-5′
2019
Lumasiran (Oxlumo)Sense: 5′-GmsAmsCmUmUmUmCfAmUfCfCfUmGmGmAmAmAmUmAmUmAm-L96-3′
Antisense: 3′-AmsCmsCmUmGmAmAmAfGmUfAmGmGmAmCfCfUmUfUmAmUmsAfsUm-5′
2020
Inclisiran (Leqvio)Sense: 5′-CmsUmsAmGmAmCmCfUmGfUmdTUmUmGmCmUmUmUmUmGmUm-L96-3′
Antisense: 3′-AmsAmsGmAmUmCfUmGfGmAfCmAfAmAfAmCfGmAfAfAfAmsCfsAm-5′
2021
Vutrisiran (Amvuttra)Sense: 5′-UmsGmsGmGmAmUmUfUmCfAfUfGmUmAmAmCmCmAmAmGmAm-L96-3′
Antisense: 3′-CmsUmsAmCmCmCmUmAfAmAfGmUmAmCmAfUmUmGfGmUmUmsCfsUm-5′
2022
Nedosiran (Rivfloza)Sense: 5′-AmsUmGfUmUfGmUmCfCfUfUfUmUfUmAfUmCfUmGmAmGmCmAmGmCm
-Cm-AdemG-AdemA-AdemA-AdemA-GmGmCmUmGmCm-3′
Antisense: 3′-GmsGmsUmAmCfAmAfCmAfGmGmAmAfAfAmAfGmAfGfsAfsCfsUm*-5′
2023
  • A, adenosine; AdemA, GalNAc aminosugar conjugated adenosine; AdemG, GalNAc aminosugar conjugated guanosine; Af, 2′-fluoroadenosine; Am, 2′-O-methyladenosine; C, cytidine; Cf, 2′-fluorocytidine; Cm, 2′-O-methylcytidine; dT, thymidine; G, guanosine; Gf, 2′-fluoroguanosine; Gm, 2′-O-methylguanosine; s, phosphorothioate; U, uridine; Uf, 2′-fluorouridine; Um, 2′-O-methyluridine; Um*, 2′-O-methyl-4’-O-((methoxy)phosphoryl)methyluridine.