Platelet-Directed Gene Therapy

Beyond their prominent role in hemostasis and thrombosis, platelets are characterized by expert functions in assisting and modulating vascular integrity, inflammatory reactions and immune responses. These pleiotropic functions are partly achieved by the release of a multitude of secretary proteins at the site of vascular injury. Since platelets can circulate throughout the body and release a number of mediators on demand, targeting platelets as a circulating delivery system would seem a reasonable approach to modify hemostasis and thrombus formation. Gene transfer in platelets requires gene transduction into hematopoietic stem cells (HSCs) using integrating vectors that directly regulate the expression of the targeted substance by a platelet-specific promoter, because platelets are anucleate cells and their precursor megakaryocytes have a limited life span. Recent studies show that gene transduction of HSCs results in sufficient genetic information been given in platelets so that they synthesize sufficient transgene products during megakaryopoiesis. Indeed, phenotype correction of a mouse model of inherited platelet disorder and hemophilia A by plateletdirected gene transduction has been demonstrated. This review highlights the cellular advantages of platelets as delivery vesicles of a specific factor, the recent advances of transgenic mice, and transduction of HSCs to establish the efficient expression of the targeted protein in platelets.