GENE THERAPY FOR B THALASSEMIA AND SICKLE CELL ANEMIA

B 型地中海贫血和镰状细胞性贫血的基因治疗

• 批准号: 2224441
• 负责人: IRVING M LONDON
• 金额: $ 19.34万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1997-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2224441
• 关键词: RNase protection assay; Retroviridae; autologous transplantation; blood cell count; bone marrow transplantation; disease /disorder model; flow cytometry; fusion gene; gene therapy; genetic enhancer element; genetic transduction; globin; hematopoietic stem cells; hemoglobin Ss; human tissue; immunofluorescence technique; laboratory mouse; neomycin; polymerase chain reaction; provirus; sickle cell anemia; southern blotting; thalassemia; tissue /cell culture; transfection /expression vector

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.

这项研究的长期目标是实现成功的基因工程。 治疗人类造血系统疾病，特别是 β地中海贫血症和镰状细胞贫血症。 我们的具体目标是： 设计新的逆转录病毒载体，用于有效选择感染的 全能造血干细胞，以实现100%的长期 移植动物的重建和完全消除非 感染细胞;感染人和鼠全能造血干细胞 来自正常和β-地中海贫血受试者的细胞与优化的逆转录病毒 转移人β珠蛋白基因和基因座控制区的载体 衍生物，并测试它们的体内性质;以及将珠蛋白 通过逆转录病毒载体的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 为以后的血液病基因治疗的临床研究奠定了基础 紊乱 该提案代表了欧文M.菲利普？伦敦 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，康妮伊夫斯和R。特里·福克斯的基思·汉弗莱斯 不列颠哥伦比亚省癌症机构的实验室和 巴黎大学