Antithrombin III messenger RNA (SERPINC1 mRNA) (SERPINC1 mRNA)

Antithrombin III mRNA, encoded by the SERPINC1 gene, is the primary template for the synthesis of antithrombin, a potent endogenous anticoagulant produced predominantly in hepatocytes (UniProt P01008). Antithrombin functions by inhibiting serine proteases in the coagulation cascade, most notably thrombin and activated Factor X (FXa), thereby preventing excessive clot formation (StatPearls, Antithrombin III Deficiency). In the context of hemophilia, where procoagulant factors are deficient, targeting antithrombin mRNA to reduce its protein levels serves as a strategy to rebalance hemostasis and promote thrombin generation (Pasi et al., NEJM 2017, PubMed: 28876928). Fitusiran is a prominent siRNA therapeutic that utilizes this mechanism by specifically targeting antithrombin mRNA in the liver via N-acetylgalactosamine (GalNAc) conjugation (Alnylam Pharmaceuticals). By lowering the "brake" on the coagulation system, this approach aims to prevent bleeding episodes in patients with Hemophilia A or B, regardless of inhibitor status (Sanofi, ATLAS Phase 3 program). Monitoring of plasma antithrombin levels and liver function is critical during therapy to manage the risks of thrombosis and hepatotoxicity (Callaghan et al., Blood 2021).

Other names

Antithrombin mRNAATIII mRNASERPINC1 transcriptSerpin family C member 1 mRNA

RNA interference (RNAi) mediated degradation of SERPINC1 mRNA in hepatocytes to reduce antithrombin protein levels and restore thrombin generation (Pasi et al., NEJM 2017).