CORE--GENE AND CELLULAR THERAPY

核心——基因与细胞治疗

• 批准号: 6646603
• 负责人: RAFAEL G AMADO
• 金额: $ 12.95万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6646603
• 关键词: AIDS; AIDS therapy; HIV infections; Retroviridae; biomedical facility; bone marrow; cell line; clinical research; cytokine; gene therapy; health science research support; hematopoietic stem cells; human subject; pathologic process; reporter genes; transfection /expression vector; virus envelope

The overall goal of this core is to provide scientific and technical support for clinical and laboratory projects that require the use of recombinant retroviral vector technology and hematopoietic stem cell purification. The specific aims are: 1. To provide technical and logistical support for the implementation of human gene therapy trials for HIV. This Core will serve as a reference source for clinicians engaged in research in the area of gene therapy for HIV infection. The Core will provide technical assistance for studies requiring BSL-3 and GLP guidelines in the following areas: I) large scale purification of hematopoietic progenitors; ii) large-scale transduction of hematopoietic progenitors; iii) assessment of vector presence in mature hematopoietic cells and in bone marrow progenitors, and iv) follow-up assays in patient samples for the development of replication competent retrovirus (RCR) according to FDA regulations. The Core will provide scientific advice in the following ares: I) FDA regulations governing the conduct of human gene therapy trials; ii) issues related to retroviral vectoring, including choice of envelope and producer cell line, manufacturing of viral supernatant under GMP conditions, titration assays,, use of cytokine combinations and other ancillary products during transduction, and iii) current guidelines and protocols available for toxicology testing in gene therapy, including assays to detect RCR and vector mediated immune responses. 2. To provide technical and logistical support to basic science research in gene therapy, hematopoiesis and pathogenesis of HIV infection. This Core will maintain stocks of HSC characterized by source, purity, gender and HLA haplotype for use in basic science projects in SCID-hu in vivo modeling experiments. The Core will also serve as a banking source for common retroviral packaging cell lines, reporter genes and packaging plasmids. The Core will also serve as a scientific and technical reference to basic science groups in the performance of laboratory assays commonly used in hematopoiesis and gene therapy research, including use of retroviral vectors, manufacturing of producer lines, isolation of highly primitive stem cell populations by functional assays and the performance of clonogenic assays. 3. To sere as an interface between clinical and basic science research groups by coordinating and regulating the use of clinical specimens in basic science research. Specimens from clinical trials will be banked and inventories in the Core, which will serve as a source of patient samples for basic sciences projects of hematopoiesis, gene therapy and HIV pathogenesis. Sample swill include CD34+ cells transduced with various anti-HIV reagents and follow-up blood and bone marrow samples from patients participating in gene therapy protocols.

该核心的总体目标是提供科学和技术 支持需要使用的临床和实验室项目 重组逆转录病毒载体技术和造血干细胞 纯化。具体目的是： 1。为实施提供技术和后勤支持 HIV的人类基因治疗试验。该核心将作为参考 从事基因治疗领域研究的临床医生的来源 艾滋病毒感染。核心将为研究提供技术帮助 在以下领域需要BSL-3和GLP指南：i）大规模 纯化造血祖细胞的纯化； ii）大规模转移 造血祖细胞； iii）评估成熟的载体存在 造血细胞和骨髓祖细胞和iv）随访 在患者样品中进行测定以开发复制能力 根据FDA法规，逆转录病毒（RCR）。核心将提供 以下ARES中的科学建议：i）管理法规 人类基因治疗试验的进行； ii）与逆转录病毒有关的问题 矢量，包括信封和生产者细胞系的选择， 在GMP条件下的病毒上清液制造，滴定 测定，使用细胞因子组合和其他辅助产品的测定 转导，以及iii）当前的准则和协议可用于 基因疗法中的毒理学测试，包括检测RCR和 向量介导的免疫反应。 2。为基础科学研究提供技术和后勤支持 在基因治疗，造血和HIV感染的发病机理中。这 核心将保持HSC的库存，其特征是来源，纯度，性别 和HLA单倍型用于体内SCID-HU的基础科学项目 建模实验。核心还将作为银行来源 常见的逆转录病毒包装细胞系，报告基因和包装 质粒。核心还将作为科学技术参考 在实验室测定的性能中，基础科学小组通常 用于造血和基因治疗研究，包括使用 逆转录病毒载体，生产线生产生产，高度隔离 原始的干细胞群体通过功能测定和性能 克隆生成测定。 3。作为临床和基础科学研究之间的接口 通过协调和调节在 基础科学研究。临床试验的标本将被库存，并 核心中的库存将作为患者样品的来源 对于造血的基本科学项目，基因疗法和HIV 发病。样品燕子包括用各种转导的CD34+细胞 抗HIV试剂以及随访的血液和骨髓样品 参加基因治疗方案的患者。