Personalised gene-targeted treatment strategies for the management of the complex genetic bleeding disorder Von Willebrand disease in stratified patient populations

Von Willebrand disease (VWD) is an inherited bleeding disorder caused by defects in Von Willebrand Factor (VWF), which promotes clot formation and arrest of bleeding. Current treatment relies on supplementing or stimulating VWF release which is ineffective in many patients due to the complex and diverse mechanisms that cause VWD. Building upon our recent advances in understanding the complex genetics behind VWD, we aim to further develop gene editing therapies targeting distinct VWF mutations using different, complementary approaches, thereby providing the first personalized treatment for VWD, by 1) develop and test therapeutic strategies with gene silencing RNAs; 2) develop and test CRISPR-Cas9 gene correction strategies and 3) develop an AAV vector for targeted delivery of gene products to the endothelium.