20. Gene Therapy for Von Willebrand Disease

  1. Augusto B. Federici MD3,
  2. Christine A. Lee MA, MD, DSc (Med), FRCP, FRCPath, FRCOGad eundem4,
  3. Erik E. Berntorp MD, PhD5,
  4. David Lillicrap MD6 and
  5. Robert R. Montgomery MD7,8
  1. Marinee K. L. Chuah PhD1,2,
  2. Inge Petrus PhD1 and
  3. Thierry VandenDriessche PhD1,2

Published Online: 21 MAR 2011

DOI: 10.1002/9781444329926.ch20

Von Willebrand Disease: Basic and Clinical Aspects

Von Willebrand Disease: Basic and Clinical Aspects

How to Cite

Chuah, M. K. L., Petrus, I. and VandenDriessche, T. (2011) Gene Therapy for Von Willebrand Disease, in Von Willebrand Disease: Basic and Clinical Aspects (eds A. B. Federici, C. A. Lee, E. E. Berntorp, D. Lillicrap and R. R. Montgomery), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781444329926.ch20

Editor Information

  1. 3

    Division of Hematology and Transfusion Medicine, L. Sacco University Hospital, Department of Internal Medicine, University of Milan, Milan, Italy

  2. 4

    University of London, London, UK

  3. 5

    Malmö Centre for Thrombosis and Haemostasis, Lund University, Skåne University Hospital, Malmö, Sweden

  4. 6

    Department of Pathology and Molecular Medicine, Richardson Laboratory, Queen's University, Kingston, ON, Canada

  5. 7

    Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA

  6. 8

    Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI, USA

Author Information

  1. 1

    Flanders Institute for Biotechnology (VIB), Vesalius Research Center, University of Leuven, Leuven, Belgium

  2. 2

    Faculty of Medicine and Pharmacy, University Hospital Campus Jette, Free University of Brussels (VUB), Brussels, Belgium

Publication History

  1. Published Online: 21 MAR 2011
  2. Published Print: 25 MAR 2011

ISBN Information

Print ISBN: 9781405195126

Online ISBN: 9781444329926



  • von Willebrand factor;
  • von Willebrand disease;
  • endothelial cell;
  • megakaryocyte;
  • platelet;
  • liver;
  • hemostasis;
  • thrombosis;
  • gene therapy


von Willebrand disease (VWD) is an attractive target disease for gene therapy. Both ex vivo and direct in vivo gene therapy approaches are being developed based on viral or non-viral gene delivery vectors. Since endothelial cells and megakaryocytes and their platelet progeny normally express von Willebrand factor (VWF), they constitute logical targets for gene therapy of VWD. Indeed, gene transfer into endothelial cells from dogs suffering from type 3 VWD using lentiviral vectors can result in de novo expression of adequately processed, fully functional VWF. However, even ectopic VWF expression in hepatocytes results in functional VWF that can correct the bleeding diathesis in VWF-deficient VWD mouse models. Despite this progress and early proof-of-concept studies, there is still a need to develop robust and safe gene therapy approaches for VWD, which would need to be validated in large animal models before moving forward with human clinical trials.