F8 and Associated Diseases
With well-trained technical and advanced platforms, Creative Biolabs can provide high-quality customer service in the field of gene therapy and offer the most appropriate research strategies to best fit your project.
Overview of F8
Factor VIII (F8, also known as anti-hemophilic factor) is an essential blood-clotting protein encoded by the F8 gene located on the X chromosome in humans. Factor VIII proteins have six domains called A1, A2, B, A3, C1, and C2. F8 is produced in liver sinusoidal cells and all the endothelial cells except the liver. When bound to the molecule called von Willebrand factor, the inactive form of F8 circulates in the bloodstream. F8 is activated and separated from von Willebrand factor when the injury of blood vessels occurs. Activated F8 interacting with Factor IX can induce a series of chemical reactions and form a blood clot in response to the injury.
F8 in Disease
People with high levels of F8 will increase the risks of hemophilia A, venous thromboembolism, and pulmonary embolism.
- Hemophilia A
F8 deficiency is associated with Hemophilia A, which is a genetically inherited X-linked bleeding disorder. In a rat model, the C-terminal part of the A3 domain of F8 is edited to form a premature translational stop. The premature F8 fails to form blood coagulation. In this homozygous rat model, the activated F8 can’t be detected and hemorrhagic episodes occur spontaneously, together with a prolonged activated partial thromboplastin time and clot formation time compared with the wild type. Recombinant F8 can normalize the activated partial thromboplastin time and clot formation time in a dose-dependent pathway.
- Venous thromboembolism
The gene copy number of F8 is associated with venous thromboembolism (VTE). VTE is a multifactorial disease with the characteristic of deep vein thrombosis. In VTE patients, the expression of F8 is significantly high than the healthy ones. The gene copy number of F8 in VTE patients is higher than the one in healthy controls, which is corresponding to the higher plasma factor 8 levels. High plasma F8 levels may cause deep venous thrombosis and be regarded as a prevalent risk factor for VTE.
Fig.1 Higher F8 activity exists in VTE patients than in healthy individuals. (Shen, 2013)
F8 deficiency can result in hemophilia A, whereas high copies of F8 may contribute to VTE. As a frontier biotech service provider, Creative Biolabs can provide the best-characterized and detailed services of gene therapy for our clients. All of the designed strategies are conducted by experienced technicians and advanced techniques. Please feel free to contact us for more about your F8 project.
References
- Nielsen, L. N.; et al. A novel F8 −/− rat as a translational model of human hemophilia A. J Thromb Haemost. 2014, 12: 1274–1282.
- Shen, W.; et al. Copy number variations of the F8 gene are associated with venous thromboembolism. Blood Cells, Molecules, and Diseases. 2013, 50: 259–262.
