Coagulation factor XI mRNA (FXI mRNA)

Coagulation factor XI (FXI) mRNA is the precursor for the FXI protein, a serine protease zymogen synthesized almost exclusively in the liver (hepatocytes). FXI plays a pivotal role in the intrinsic pathway of the coagulation cascade, where it serves to amplify thrombin generation after the initial trigger of the extrinsic pathway (Liu et al., 2021). Because FXI is more involved in the stabilization and growth of a thrombus than in the initial formation of a primary hemostatic plug, it has emerged as a promising target for safer anticoagulation (Buller et al., 2015). Therapeutic agents such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are designed to bind specifically to FXI mRNA in hepatocytes, leading to its degradation and a subsequent reduction in circulating FXI protein levels (Heitmeier et al., 2022). This approach aims to provide robust protection against thromboembolic events, such as venous thromboembolism and stroke, while maintaining a superior safety profile regarding bleeding complications compared to conventional anticoagulants (Hsu et al., 2021). Clinical development is particularly focused on patients with high thrombotic risk and high bleeding risk, such as those with end-stage renal disease or atrial fibrillation (Verhamme et al., 2021).

Other names

F11 mRNAPlasma thromboplastin antecedent mRNAFactor 11 mRNA

Antisense oligonucleotides (ASOs) bind to the target mRNA and induce its degradation via RNase H1, while small interfering RNAs (siRNAs) utilize the RNA-induced silencing complex (RISC) to cleave the mRNA, both resulting in reduced synthesis of the Factor XI protein in hepatocytes (Buller et al., 2015; Liu et al., 2021).