Table 2.
Difference in mode of action.
| Active ingredient (Company) | Patisiran (Alnylam) | Tozinameran (Pfizer/BioNTech), Elasomeran (Moderna) |
|---|---|---|
| Drug substance | siRNA | mRNA |
| Strand | double strand | single strand |
| RNA length | 42 (21 + 21) | 4284 (Tozinameran)a |
| Base modification | 2ʹ-OMe-uridine, 2ʹ-OMe-cytosine | N1-methyl-pseudouridine |
| Purpose of base modification | suppress the innate immune response to mitigate off-target effect | suppress the innate immune response to increase protein production |
| Mode of action | stop production of target protein by degrading mRNA | initiate production of target protein by supplying mRNA, which triggers the adaptive immunity |
| Target protein | Transthyretin (TTR) | spike of SARS-CoV-2b |
| Endogenous machinery | RNA interference | translation |
| Location of machinery | cytoplasm | cytoplasm |
| Primary target cell of LNP | hepatocytes | antigen presenting cells (APCs) |
LNP, lipid nanoparticles; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
a
Structure of Elasomeran is not described in detail.
b
Target spike proteins are modified by 2 proline substitutions to produce prefusion-stabilized SARS-CoV-2 spike protein.