Generating HIV resistant cells from conditionally transformed HSC cell lines

从条件转化的 HSC 细胞系中产生 HIV 抗性细胞

基本信息

批准号：
7419068
负责人：
YOSEF REFAELI
金额：
$ 16.12万
依托单位：
TAIGA BIOTECHNOLOGIES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-19 至 2010-09-18
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7419068
关键词：
AIDS therapy Adult Animals Arts Biological Assay Blood Blood Cells Bone Marrow Bone Marrow Stem Cell Bone Marrow Stem Cell Transplantation Bone Marrow Transplantation CCR5 gene CXCR4 gene Cell Line Cell Lineage Cell Transplantation Cells Chemokine (C-C Motif) Receptor 5 Child Clinical Clinical Trials Data Engraftment Generations Goals HIV HIV-1 Hematopoietic stem cells Human Immune Immune system Immunologic Deficiency Syndromes In Vitro Individual Infection Laboratories Leukapheresis Lymphocyte Malignant Neoplasms Marrow Methods Methylcellulose Modeling Monitor Mus Patients Phase Phase I Clinical Trials Primates Production Property Public Health Radiation Receptor Gene Research Resistance Resources Source Standards of Weights and Measures Stem cell transplant Stem cells T-Lymphocyte Technology Testing Therapeutic Transduction Gene Transplantation Umbilical Cord Blood Validation Virus Virus Diseases Work base cell type chemotherapy clinical application day drug development graft vs host disease graft vs host reaction human stem cells in vivo macrophage mouse model new technology peripheral blood pluripotency receptor reconstitution small hairpin RNA tool vector

项目摘要

DESCRIPTION (provided by applicant): Using a method of retroviral gene transduction we have been able to generate conditionally immortalized long-term hematopoietic stem cell lines from primary mouse bone marrow stem cells. Phase I of this project includes testing the same technology in human cells and the subsequent analysis of those cells in the laboratory and in mice. In addition, the project includes knockdown of HIV-1 co-receptors to generate HIV-1 resistant cells in a mouse model. The method to genetically modify the long-term hematopoietic stem cell lines includes state-of-the-art vector transduction with shRNA containing constructs. Phase II of the project will entail testing this approach in a primate model and optimizing large-scale production of genetically-modified conditionally-immortalized long-term hematopoietic stem cells for testing in clinical trials. This project seeks to refine appropriate methods to genetically manipulate conditionally immortalized hematopoietic stem cell lines to generate HIV-1 resistant cells. Once these methods have been established for the human, the long-term goal to benefit public health will be to use these cells for treating HIV-1 infected patients to re-establish a functional immune system that is protected from endogenous or exogenous sources of HIV.

描述（由申请人提供）：使用逆转录病毒基因转导方法，我们已经能够从原代小鼠骨髓干细胞产生条件永生化的长期造血干细胞系。该项目的第一阶段包括在人体细胞中测试相同的技术，以及随后在实验室和小鼠中对这些细胞进行分析。此外，该项目还包括敲低 HIV-1 辅助受体，以在小鼠模型中产生 HIV-1 耐药细胞。对长期造血干细胞系进行基因修饰的方法包括使用含有 shRNA 的构建体进行最先进的载体转导。该项目的第二阶段将需要在灵长类动物模型中测试这种方法，并优化转基因条件永生化长期造血干细胞的大规模生产，以便在临床试验中进行测试。该项目旨在完善适当的方法，对条件永生化造血干细胞系进行基因操作，以产生 HIV-1 抗性细胞。一旦为人类建立了这些方法，造福公众健康的长期目标将是使用这些细胞治疗 HIV-1 感染患者，以重建功能性免疫系统，免受内源性或外源性 HIV 的侵害。