甲型血友病（HA）是由于凝血因子VIII（FⅧ）的蛋白编码基因F8突变引起的常见血液遗传病，患者会自发性反复出血或出血不止进而危及生命。由于长期输注FⅧ会产生同种异源抗体而导致输注的FⅧ失效，因此基因治疗是目前的根治方法。但目前临床的基因治疗普遍转染效率低，FⅧ水平无法达到治疗效果。我们前期研究发现利用αIIb启动子诱导巨核细胞上表达FⅧ储存于血小板的方法，能使FⅧ在小鼠体内持续表达。这种基于血小板的基因治疗与血小板上的功能蛋白关系密切，如血小板上的VWF将直接影响我们基因治疗的成效。而位于血小板上的GPIb蛋白在凝血过程中首先与VWF结合进而启动凝血。那GPIb在血小板αIIb启动子介导的HA基因治疗中是否起重要作用？本研究将通过建立GPIb缺陷的血友病小鼠模型，并进行基因治疗，然后对治疗的效果和对FⅧ的免疫耐受性进行评估，探索GPIb蛋白在我们基因治疗中的作用，为临床应用提供科学依据。

Hemophilia A is a genetic disease because of the mutation of the encoding gene (F8) of the coagulation factor VIII. Patients suffer from frequent spontaneously or traumatic bleeding, sometimes lead to death. After long-term infusion of FVIII, the patients would develop anti-FVIII antibody, which lead to treatment failure. So gene therapy is the only way for radical cure. Currently, the efficiency of HA gene therapy in clinical is not good. In our study, we use of the alpha IIb promoter to target FVIII specifically expressed in platelets, enabling FVIII protein to continuously expressed and reach normal level in mice. In our published research, we have shown that VWF on the platelets affect the efficacy of our gene therapy. In the process of coagulation, GPIb protein first combines with VWF to initiate the coagulation process. So how GPIb affect our gene therapy? In this study, we establish GPIb-F8- mouse model, and evaluate the efficacy of gene therapy treatment. The aim of this study is to explore the effect of GPIb in our gene therapy. This study will further improve our gene therapy, and provide a better scientific basis for future clinical treatment.