Coagulation Factor X and hepatocyte surface receptors (FX-HSR)

Coagulation Factor X (FX) is a vitamin K-dependent serine protease synthesized in the liver that plays a central role in the blood coagulation cascade by converting prothrombin to thrombin (UniProt P00742). Beyond its role in hemostasis, FX has been identified as a critical mediator for the liver-specific uptake of certain viral vectors, particularly Adenovirus serotype 5 (Ad5). In the bloodstream, the Gla domain of FX binds to the hexon protein of the virus, and the complex subsequently interacts with hepatocyte surface receptors, primarily Heparan Sulfate Proteoglycans (HSPGs) and Low-density lipoprotein receptor-related protein 1 (LRP1) (Waddington et al., 2008, Cell). This interaction leads to the sequestration of viral gene therapies in the liver, often resulting in significant hepatotoxicity and reduced delivery to intended extrahepatic tissues (Kalyuzhniy et al., 2008, PNAS). Consequently, this pathway is a major focus for engineering liver-blind viral vectors or developing pharmacological interventions to block the FX-mediated bridge. Clinically, FX itself is the primary target for Direct Oral Anticoagulants (DOACs) like rivaroxaban and apixaban, which are used to treat and prevent thromboembolic diseases (PubChem CID 6433119). Understanding the dual role of FX in both coagulation and viral trafficking is essential for optimizing gene therapy safety and efficacy.

Other names

Factor X-HSPG interactionAd5-FX-LRP1 axisFX-mediated hepatocyte targetingStuart-Prower factor interaction

Direct inhibition of Factor Xa enzymatic activity or competitive inhibition of the Factor X-viral vector complex binding to hepatocyte receptors.