GENE THERAPY FOR B THALASSEMIA AND SICKLE CELL ANEMIA

这项研究的长期目标是获得成功的基因 人类造血系统疾病的治疗，特别是 β地中海贫血和镰状细胞性贫血。我们的具体目标是： 设计新型逆转录病毒载体高效筛选感染者 全能造血干细胞，从而实现100%的长期 移植动物的重建和完全消除非 感染细胞；感染人和小鼠的全能造血干细胞 来自正常和β-地中海贫血患者的细胞，经优化后的逆转录病毒 人β-珠蛋白基因转移载体及其基因座控制区 并测试它们的体内性质；以及转移珠蛋白 利用逆转录病毒载体进行基因治疗镰状细胞病。这些 临床前研究旨在提供科学和技术上的 为后续这些血液病的基因治疗的临床研究奠定基础 精神错乱。 这项提议代表了欧文·M·伦敦和菲利普之间的合作 哈佛-麻省理工学院健康科学部的LeBoulch和Dorothy Tuan 和麻省理工学院的技术，Terry Fox的康妮·伊夫斯和R·基思·汉弗莱斯 不列颠哥伦比亚省癌症研究所的实验室和伊夫·布扎德的 巴黎十二大学。

The long term objective of this research is to achieve successful gene therapy of human diseases of the hematopoietic system, specifically of the beta thalassemias and sickle cell anemia. Our specific aims are: to design new retroviral vectors for efficient selection of infected totipotent hematopoietic stem cells so as to achieve 100 percent long-term reconstitution of transplanted animals and complete elimination of non- infected cells; to infect human and murine totipotent hematopoietic stem cells from normal and beta-thalassemic subjects with optimized retroviral vectors for transferring human beta globin gene and Locus Control Region derivatives and to test their in vivo properties; and to transfer a globin gene by retroviral vectors for gene therapy of sickle cell disease. These pre-clinical studies are designed to provide the scientific and technologic basis for subsequent clinical studies of gene therapy of these hematologic disorders. This proposal represents a collaboration between Irving M. London, Philippe LeBoulch and Dorothy Tuan of the Harvard-MIT Division of Health Sciences and Technology of MIT, Connie Eaves and R. Keith Humphries of the Terry Fox Laboratories of the British Columbia Cancer Agency, and Yves Beuzard of the University of Paris XII.