Indeed, immune responses against FVIII are a significant concern in both protein replacement therapy and gene therapy of hemophilia A. Taking the advantage of platelets' unique biological capacities as a storage cargo and delivery vehicle (43), we have developed a platelet-specific gene therapy protocol that can efficiently restore hemostasis and engender profound immune tolerance to the therapeutic products in hemophilia models (31–33). This evidence concerns the gene F8 and hemophilia.