RETROVIRAL MEDIATED GLOBIN GENE THERAPY

描述：（改编自申请人摘要）申请人是 探索纠正临床表现的方法 使用体细胞基因疗法治疗血红蛋白病。 alpha-LCR将 在逆转录病毒转移中与人β-珠蛋白样基因偶联 向量。申请人亦会利用最近 在β-珠蛋白基因的IVSII中鉴定出不稳定序列， 构建更有效的载体来表达这个基因。后 载体已经被工程化，申请人将测试它们的功效 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。对骨髓细胞的研究将测试 该载体具有扩增多能干细胞的能力。工作 将通过审查表达能力来确定上限， 逆转录病毒转导的地中海贫血和镰状细胞小鼠模型 β-球蛋白样基因。

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.