Project: An innovating platform using miniplasmids, transposon and S/MAR for von Willebrand disease gene therapy

Type 3 von Willebrand Disease is caused by the absence of von Willebrand factor, leading to severe hemophilia. Its prevalence is inferior to 5/1000000, and its treatment necessitates a high blood concentration of von Willebrand factor. A gene therapy ensuring a highly efficient and prolonged in vivo production of the missing factor would be of particular benefit for the patients. Liver is the optimal organ for the secretion and systemic distribution of a therapeutic transgene product. The TRANSPOSMART consortium will assemble and fine-tune “cutting edge” gene therapy tools in combination with either non-integrating or transposon-based integrating approaches for therapeutic protein secretion by the liver. Each partner is expert in one of the key technologies to be integrated: pFAR biosafe miniplasmids, hyperactive Sleeping Beauty transposon system SB100X, adenovirus/ transposon hybrid technology, Scaffold/Matrix-Attachment Region, and gene delivery to the liver by either plasmid hydrodynamic or adenoviral techniques. Our consortium gathers recognized leaders in the field of gene therapy and of von Willebrand disease physiology. The consortium will apply the added value of this integrated platform to mouse and dog models of von Willebrand Disease. Our approach offers an optimal strategy to deliver and express the von Willebrand factor in the liver, for blood secretion. The dog large animal study represents a promising translational step toward a clinical trial for the gene therapy of von Willebrand Disease, and ultimately for a large number of gene therapy applications.

Network E-Rare-2
Call 3rd Joint Call for Research Projects on Rare Diseases

Project partner

Number Name Role Country
1 Centre National de la Recherche Scientifique (CNRS) Coordinator France
2 KU Leuven Campus Kortrijk Partner Belgium
3 Max Delbruck Center for Molecular Medicine Partner Germany
4 Ludwig-Maximilians-Universität Munich / Max von Pettenkofer-Institut Partner Germany
5 University of Patras, Medical School Partner Greece
6 Hadassah Hebrew University Hospital Partner Israel