1 Bioengineering of Coagulation Factor VIII for Improved Secretion

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Bioengineering of coagulation factor VIII for improved secretion.

Factor VIII (FVIII) functions as a cofactor within the intrinsic pathway of blood coagulation. Quantitative or qualitative deficiencies of FVIII result in the inherited bleeding disorder hemophilia A. Expression of FVIII (domain structure A1-A2-B-A3-C1-C2) in heterologous mammalian systems is 2 to 3 orders of magnitude less efficient compared with other proteins of similar size compromising rec...

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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Bioengineering of coagulation factor VIII for improved secretion

Factor VIII (FVIII) functions as a cofactor within the intrinsic pathway of blood coagulation. Quantitative or qualitative deficiencies of FVIII result in the inherited bleeding disorder hemophilia A. Expression of FVIII (domain structure A1-A2-BA3-C1-C2) in heterologous mammalian systems is 2 to 3 orders of magnitude less efficient compared with other proteins of similar size compromising reco...

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Bioengineering coagulation factors for improved hemophilia treatments☆

The implementation of prophylaxis with regular factor VIII (FVIII) replacement for patients with hemophilia radically changed the clinical presentation of this condition, from a disease characterized by progressive disabling musculoskeletal complications, to one compatible with an active and virtually normal lifestyle. In Brazil, although most adults with severe hemophilia still suffer the impa...

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Bioengineering of coagulation factor VIII for efficient expression through elimination of a dispensable disulfide loop.

BACKGROUND Heterologous expression of factor VIII (FVIII) is about two to three orders of magnitude lower than similarly sized proteins. Bioengineering strategies aimed at different structural and biochemical attributes of FVIII have been successful in enhancing its expression levels. OBJECTIVE Disulfide bonds are vital to the proper folding, secretion and stability of most secretory proteins...

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The Effects of Novel Mutations in A1 Domain of Human Coagulation Factor VIII on Its Secretion Level in Cultured Mammalian Cells

Inefficient secretion of the human coagulation factor (hFVIII) in mammalian expression systems is one ofthe main causes of the hFVIII low expression level, attributed to its interaction with a chaperone known asBiP/GRP78. In order to improve secretion efficiency of the hFVIII, based on the higher secretion level of theporcine FVIII and analysis of the hFVIII A110 region, that ...

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ژورنال

عنوان ژورنال: Pediatric Research

سال: 2005

ISSN: 0031-3998,1530-0447

DOI: 10.1203/00006450-200510000-00031