When factor VIII/von Willebrand factor (FVIII/vWF) is chromatographed on 4% agarose in 0.25 M CaCI2. the procoagulant activity partially separates from the void volume protein peak. If FVIII/vWF is reacted with thrombin prior to chromatography, both the magnitude and resolution of the proe.oagulant activity peak are greatly increased. These observations suggest that activated species of FVIII/v...

The cellular source of coagulation factor VIII (FVIII) remains controversial. Like many coagulation proteins, FVIII is produced in the liver, and FVIII synthesis has long been associated with hepatocytes. But extrahepatic synthesis also occurs, and mounting evidence suggests that hepatocytes are not responsible for FVIII production. To determine the tissue that synthesizes FVIII, we developed a...

Inefficient intracellular protein trafficking is a critical issue in the pathogenesis of a variety of diseases and in recombinant protein production. Here we investigated the trafficking of factor VIII (FVIII), which is affected in the coagulation disorder hemophilia A. We hypothesized that chemical chaperones may be useful to enhance folding and processing of FVIII in recombinant protein produ...

Administration of human factor VIII (FVIII) to FVIII knockout hemophilia mice is a useful small animal model to study the physiologic response in patients iatrogenically immunized to this therapeutic protein. These mice manifest a robust, T cell-dependent, antibody response to exogenous FVIII treatment, even when encountered through traditionally tolerogenic routes. Thus, FVIII given via these ...

Replacement of the missing factor VIII (FVIII) is the current standard of care for patients with hemophilia A. However, the short half-life of FVIII makes frequent treatment necessary. Current efforts focus on the development of longer-acting FVIII concentrates by introducing chemical and genetic modifications to the protein. Any modification of the FVIII protein, however, risks increasing its ...

Gene transfer of a factor VIII (FVIII) plasmid into hemophilia A (HemA) mice achieved supraphysiologic FVIII expression, but triggered production of high-titer FVIII-specific antibodies and loss of functional FVIII activity. To test whether FVIII-specific regulatory T cells (Tregs) can modulate immune responses against FVIII, we developed a HemA mouse model in which all T cells overexpressed Fo...

Hemophilia A is caused by a deficiency of blood coagulation factor VIII (FVIII) and has been widely discussed as a candidate for gene therapy. While the natural canine model of hemophilia A has been valuable for the development of FVIII pharmaceutical products, the use of hemophiliac dogs for gene therapy studies has several limitations such as expense and the long canine generation time. The r...

Von Willebrand Disease (VWD) is the most common inherited bleeding disorder, caused by a deficiency or abnormality of the Von Willebrand Factor (VWF). The mainstays of treatment are therapy with Desmopressin (DDAVP) and replacement therapy with Factor VIII-containing VWF product (FVIII/VWF). Therapy with FVIII/VWF can be administered as Long-term prophylaxis (LTP) in the more severe forms of th...

Background and novelty Coagulation Factor VIII (FVIII) is an essential cofactor in the blood coagulation cascade. Inability to produce functional FVIII results in haemophilia A which can be treated with recombinant FVIII [1]. Chinese Hamster Ovary (CHO) cells are the most used cell line for producing complex biopharmaceuticals due to its ability to perform complex post-translational modificatio...

Prophylaxis and treatment of inherited clotting disorder hemophilia A requires regular administration of factor VIII. Recombinant factor VIII, which is produced in CHO or BHK cells, is equivalent to the plasma-derived one and is prevalent in current clinical practice in developed countries. Development of a biosimilar recombinant FVIII requires the creation of a highly productive clonal cell li...