Semin Thromb Hemost 2010; 36(5): 510-521
DOI: 10.1055/s-0030-1255445
© Thieme Medical Publishers

Structure and Function of a Recombinant von Willebrand Factor Drug Candidate

Peter L. Turecek1 , Gerald Schrenk1 , Hanspeter Rottensteiner1 , Katalin Varadi1 , Edouard Bevers3 , Peter Lenting4 , Nicola Ilk2 , Uwe B. Sleytr2 , Hartmut J. Ehrlich1 , Hans Peter Schwarz1
  • 1Baxter BioScience, Vienna, Austria
  • 2Department of NanoBiotechnology, BOKU-University of Natural Resources and Applied Life Sciences, Vienna, Austria
  • 3Cardiovascular Research Institute Maastricht, Department of Biochemistry, Maastricht, The Netherlands
  • 4INSERM U770, Le Kremlin-Bicêtre, France
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Publication History

Publication Date:
15 July 2010 (online)

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ABSTRACT

The complex structure, large size, and multiple posttranslational modifications of von Willebrand factor (VWF) presented a technological challenge for the production of recombinant VWF (rVWF). Nonetheless, we developed an rVWF product for treating von Willebrand disease, whereupon rVWF is coexpressed with recombinant factor VIII (rFVIII) in Chinese hamster ovary cells used to produce rFVIII for the treatment of hemophilia A. Here we describe the characterization of the structure and function of the rVWF drug product, with a focus on its in vitro platelet aggregation and matrix protein binding functions. Electron microscopy and multimer analysis revealed a highly organized structure for the rVWF protein, with a homogeneous multimer distribution including ultrahigh molecular weight multimers. The specific activity for binding to collagen and platelets mediated by ristocetin is higher in rVWF than in commercial plasma-derived VWF-FVIII complex products. The affinity and binding capacity of rVWF to FVIII is comparable to VWF in plasma. rVWF effectively binds to platelets and promotes platelet adhesion under shear stress similar to VWF in human plasma.

REFERENCES

Peter L TurecekPh.D. 

Baxter Innovations GmbH, Industriestrasse 67

1220, Vienna, Austria

Email: peter_turecek@baxter.com