广西是地贫的高发区，重型β地贫临床缺乏有效的治疗手段，基因治疗已成为临床的希望。我们前期在体外利用小RNA干扰（siRNA）技术调控α珠蛋白基因的表达，能纠正β地贫病人红细胞α与非α珠蛋白链的合成不平衡,减少红细胞凋亡。我们还发现地贫患者BCL11A基因位点rs1427407，rs766432与HbF水平有关。本课题拟以β地贫病人的CD34+细胞为对象，采用siRNA及慢病毒载体基因转染技术，分别靶向下调Bcl11A、SOX6及KLF1的表达,运用定量PCR技术、高效液相技术观察其激活γ珠蛋白基因表达，诱导HbF合成的作用。此外，观察靶向下调Bcl11A、SOX6及KLF1的表达对β地贫病人红细胞其它珠蛋白基因（ζ、α、ε、δ、β）表达的影响；采用Western Blot技术观察Bcl11A、SOX6及KLF1之间的相互影响，探讨其作用机制，为临床靶向治疗β地贫提供实验基础。

β-thalassemia is one of the most common hereditary hemolytic diseases in Guangxi. Genetic therapy is a promising strategy for thalassemia. We have reported reducting a-globin synthesis and restoring a and non-a globin balance by using a small interfering RNA (siRNA)in β-thalassemic erythroid cells.We found the rs1427407 and rs766432 of BCL11A were associated with Hb F level in thalassemia patients. In this study,we plan to use an in vitro model of human erythropoiesis to assay for enhanced production of HbF after gene delivery into CD34 cells obtained from mobilized peripheral blood of normal adults or steady-state bone marrow from patients with β-thalassemia major. Lenti-viral vectors encoding a siRNA targeting the γ-globin gene repressor as BCL11A, SOX6 and KLF1 are tested. The mRNA of γ-globin and other globin(ζ,α,ε,δ,β) are assessed using the qPT-PCR method. The HbF, HbA and HbA2 levels are tested by high-performance liquid chromatography (HPLC). Western Blot analysis for BCL11A, SOX6 and KLF1 are done. The purpose of our study is to confirm the BCL11A, SOX6 and KLF1 as a therapeutic target for reactivation of HbF in Chinese β-thalassemia patients.