Coagulation factor XI messenger RNA (FXI mRNA) (FXI mRNA)

Coagulation factor XI (FXI) messenger RNA is the genetic template for the synthesis of the FXI protein, a serine protease essential to the intrinsic pathway of the coagulation cascade (UniProt, 2024). FXI contributes significantly to the amplification of thrombin generation and the stabilization of fibrin clots, which are key processes in the development of pathological thrombosis (Hebbbel et al., 2021, Blood). Because individuals with FXI deficiency (Hemophilia C) experience only mild bleeding symptoms, targeting FXI mRNA is viewed as a strategy to decouple antithrombotic efficacy from bleeding risk (Buller et al., 2015, NEJM). Therapeutic agents such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are designed to bind specifically to FXI mRNA in the liver, the primary site of FXI production (Liu et al., 2021, Journal of Hematology & Oncology). This binding triggers the degradation of the mRNA via RNase H1 or the RNA-induced silencing complex (RISC), thereby reducing the levels of circulating FXI protein (Crooke et al., 2021, Nature Reviews Drug Discovery). Clinical applications for these therapies include the prevention of venous thromboembolism in surgical patients and the reduction of stroke risk in patients with atrial fibrillation (ClinicalTrials.gov, 2024). By lowering the systemic concentration of FXI, these drugs provide a sustained anticoagulant effect that can be monitored through plasma FXI activity assays (Heitmeier et al., 2022, Journal of Thrombosis and Haemostasis). Overall, FXI mRNA represents a novel and potent target for next-generation anticoagulants aimed at improving the safety profile of long-term thromboprophylaxis (Ionis Pharmaceuticals, 2023).

Other names

F11 mRNAFactor XI mRNAPlasma thromboplastin antecedent mRNA

Antisense inhibition or RNA interference leading to mRNA degradation and reduced protein synthesis