Coagulation factor XI (FXI) mRNA (FXI mRNA)

Coagulation factor XI (FXI) is a zymogen of a serine protease that is synthesized primarily by hepatocytes in the liver and plays a pivotal role in the intrinsic pathway of blood coagulation (UniProt P03951). FXI mRNA in hepatocytes is the specific target for RNA-targeted therapies, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), which aim to reduce the hepatic production of FXI protein (PubMed 34879187). By lowering the levels of circulating FXI, these therapies inhibit the amplification of the coagulation cascade, thereby preventing the formation of pathological thrombi (PubMed 25485698). This approach is being investigated for the prevention of venous thromboembolism (VTE) and stroke, particularly in high-risk populations like those with end-stage renal disease or undergoing major orthopedic surgery (PubMed 34133852). Unlike traditional anticoagulants, targeting FXI mRNA is hypothesized to decouple thrombosis from hemostasis, potentially offering a lower risk of clinically significant bleeding (PubMed 28838935). Drugs like fesomersen and ovemetersen utilize this mechanism to achieve sustained reductions in FXI activity through infrequent dosing (PubMed 34879187). The specificity of these agents for hepatic mRNA ensures that the reduction in FXI is localized to the primary site of synthesis, minimizing off-target effects in other tissues (PubMed 34133852).

Other names

F11 mRNAFactor XI messenger RNAPlasma thromboplastin antecedent mRNAF11 transcript

Antisense oligonucleotide-mediated mRNA degradation or RNA interference (siRNA) to inhibit the translation of Coagulation factor XI protein in hepatocytes.