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: 2224440
• 负责人: IRVING M LONDON
• 金额: $ 20.03万
• 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/2224440
• 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获得成功的基因 治疗人类造血系统疾病，特别是造血系统疾病 β地中海贫血和镰状细胞性贫血。 我们的具体目标是： 设计新的逆转录病毒载体以有效选择感染者 全能造血干细胞，从而达到100%长期 移植动物的重建和完全消除非 受感染的细胞；感染人和鼠全能造血干 来自正常和β地中海贫血受试者的细胞，经过优化的逆转录病毒 用于转移人β珠蛋白基因和基因座控制区的载体 衍生物并测试其体内特性；并转移珠蛋白 基因通过逆转录病毒载体用于镰状细胞病的基因治疗。 这些 临床前研究旨在提供科学技术 为后续这些血液病基因治疗的临床研究奠定了基础 失调。 该提案代表了 Irving M. London、Philippe 之间的合作 哈佛-麻省理工学院健康科学部的 LeBoulch 和 Dorothy Tuan 麻省理工学院的技术与技术、Terry Fox 的 Connie Eaves 和 R. Keith Humphries 不列颠哥伦比亚省癌症机构实验室和 Yves Beuzard 实验室 巴黎第十二大学。