This research proposal falls within the scope of the LSBR as it includes fundamental research and experimental investigations focused on the blood coagulation protein von Willebrand factor. In addition, we specifically focus on targeting the cells of the vessel wall, i.e., endothelial cells to develop a therapeutic for the bleeding disorder von Willebrand disease.
Expected outcome
Objective 1: We expect to have highly active and allele-selective lead siRNAs that will form the starting point for a patent application and further clinical development.
Objective 2: Using the humanized VWF mouse, we expect to have insight into the safety and off-target effects of an siRNA alike our lead allele-selective siRNAs.
Objective 3: We expect to have a first insight into whether patient ECFCs can be transplanted into immunodeficient mice and that the subsequent ECFC-produced VWF can be monitored and targeted by (allele-selective) siRNAs targeting VWF.
Future perspective: With the results and findings following from the studies in this project, we aim to further develop the allele-selective siRNAs for clinical application in the context of silencing the mutant VWF allele in VWD.