RETROVIRAL MEDIATED GLOBIN GENE THERAPY

描述：(改编自申请人摘要)申请人为 临床表现矫治方法的探讨 利用体细胞基因疗法治疗血红蛋白疾病。阿尔法-LCR将 在逆转录病毒转移中与人β-珠蛋白样基因偶联 向量。申请人还将利用最近的 鉴定β-珠蛋白基因IVSII中的不稳定序列 构建能够转导该基因的更有效的载体。在那之后 已经设计了载体，申请者将测试它们的有效性 在许多生命系统中，包括细胞系和骨骼 短期培养的骨髓细胞。使用BM细胞的工作将测试 载体转导多能干细胞的能力。这项工作 将通过检查在 逆转录病毒转导的地中海贫血和镰状细胞小鼠模型 类似β-珠蛋白的基因。

DESCRIPTION: (Adapted from Applicant's Abstract) The Applicant is exploring approaches to correct the clinical manifestations of hemoglobinopathies using somatic cell gene therapy. The alpha-LCR will be coupled with human beta-globin like genes in retroviral transfer vectors. The Applicant will also take advantage of the recently identified destabilizing sequence in IVSII of the beta-globin gene to construct more efficient vectors that can transduce this gene. After the vectors have been engineered, the Applicant will test their efficacy in a number of living systems, including cell lines as well as bone marrow cells in short-term culture. The work with BM cells will test the ability of the vector to transduce pluripotent stem cells. The work will be capped off by examining the capacity for expression in thalassemic and sickle cell mouse models of the retrovirally transduced beta-globin like genes.