Research advances on platelet-targeted gene therapy for hemophilia A

Abstract

Gene therapy can correct the coagulation disorder permanently which can be a promising alternative for hemophilia A (HA) patients. There could be different targeted cells of human for gene therapy of HA. To solve some questions of hepatocyte-targeted gene therapy, platelet-targeted gene therapy with the FⅧ expression restricted in platelets has been developed in recent years. Platelet-targeted gene therapy strategy has been developed, in which FⅧ expression is driven by various platelet-specific promoters such as platelet glycoprotein alpha Ⅱb promoter, glycoprotein Ⅰb promoter and platelet factor-4 promoter. This gene therapy strategy has been proved to have advantages in many ways. Firstly, a substantial amount of FⅧ had potent effects to promote hemostasis and activate coagulation, which were accumulated at the sites of injury or bleeding. Then, FⅧ is stored in the alpha-granules of platelets, which greatly reduces the exposure time of FⅧ in the blood circulation, reduces the production of autoantibodies and the opportunity for FⅧ and autoantibodies. This review summarizes studies on platelet-specific gene therapy for HA in recent years. Key words: Hemophilia A; Genetic therapy; Platelet targeted; FⅧ ectopic expression; Platelet activation