Prolonged in-vivo half-life of factor VIIa by fusion to albumin
| Autor: | Wiegand Lang, Stefan Schulte, Thomas Weimer, Ulrich Kronthaler, Uwe Liebing, Wilfried Wormsbächer |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Recombinant Fusion Proteins
DNA Recombinant Factor VIIa In Vitro Techniques Pharmacology Hemophilia A Protein Engineering Haemophilia Thromboplastin law.invention Pharmacokinetics In vivo law Animals Humans Medicine Serum Albumin Hemostasis Base Sequence biology Coagulants business.industry Albumin Wild type Hematology Surface Plasmon Resonance medicine.disease Fusion protein Recombinant Proteins Rats Thrombelastography Recombinant factor VIIa Immunology biology.protein Recombinant DNA business Half-Life Protein Binding |
| Zdroj: | Thrombosis and Haemostasis. 99:659-667 |
| ISSN: | 2567-689X 0340-6245 |
| Popis: | SummaryFor the treatment of haemophilia patients with inhibitors, recombinant factor VIIa (rFVIIa) is available as a therapeutic option to control bleeding episodes with a good balance of safety and efficacy. However, the short in-vivo half-life of approximately 2.5 hours makes multiple injections necessary, which is inconvenient for both physicians and patients. Here we describe the generation of a recombinant FVIIa molecule with an extended half-life based on genetic fusion to human albumin. The recombinant FVII albumin fusion protein (rVII-FP) was expressed in mammalian cells and upon activation displayed a FVII activity close to that of wild type FVIIa. Pharmacokinetic studies in rats demonstrated that the half-life of the activated recombinant FVII albumin fusion protein (rVIIa-FP) was extended six- to sevenfold compared with wild type rFVIIa. The in-vitro and in-vivo efficacy was evaluated and was found to be comparable to a commercially available rFVIIa (NovoSeven®). The results of this study demonstrate that it is feasible to develop a half-life extended FVIIa molecule with haemostatic properties very similar to the wild-type factor. |
| Databáze: | OpenAIRE |
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