ANTI-HIV RNA TRANSDUCTION INTO BLOOD STEM CELLS IN AIDS

艾滋病患者中抗 HIV RNA 转导至血干细胞

• 批准号: 6012622
• 负责人: John A Zaia
• 金额: $ 142.7万
• 依托单位: BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6012622
• 关键词: AIDS; AIDS therapy; gene therapy; genetic transduction; hematopoietic stem cells; human immunodeficiency virus 1

This Integrated Pre-Clinical/Clinical Program from City of Hope National Medical Center (COH) proposes to develop and improve methods for genetic treatment of HIV-1 using antiviral RNA. There are three basic science projects aimed at improved gene transfer, gene expression, and HIV inhibition using retroviral and lentiviral vectors. Project 1 at Children's Hospital Los Angeles will evaluate the expression of improved vectors in monocytes and T-cells after transduction of human hematopoietic stem cells. Project 2 at the Beckman Research Institute of COH (BRICOH) will study improved stability of expression of antiviral RNA target4ed to HIV. Project 3 at BRICOH is devoted to comparative studies of improved retroviral and lentiviral vectors. In Project 4, the Clinical Trials Center will complete two comparative trials of experimental autologous stem-cell transplantation (SCT) of CD34+ peripheral blood progenitor cells (PBPC) transduced with a retrovirus encoding a double hammerhead ribozyme targeted to TAT and REV. one study, in AIDS patients with non-Hodgkin's lymphoma, utilizes an ablative marrow conditioning regimen, and the other, in healthy HIV-1 infected persons, will use hydroxyurea for partial cytoreduction of marrow. The basic science and laboratory programs are supported by three core areas. The Administrative Center, will oversee the management of the basic science and clinical studies. The DNA/RNA Analytical Lab will evaluate marrow and blood specimens post transplantation for the presence and stability of expression of the ribozyme transgene. The Virology Lab, will provide support for HIV analyses and assessment of antiviral effects of new anti-HIV RNAs.

希望之城国家医疗中心 (COH) 的这项综合临床前/临床计划提议开发和改进使用抗病毒 RNA 进行 HIV-1 基因治疗的方法。有三个基础科学项目旨在利用逆转录病毒和慢病毒载体改善基因转移、基因表达和艾滋病毒抑制。洛杉矶儿童医院的项目 1 将评估转导人类造血干细胞后单核细胞和 T 细胞中改良载体的表达。 COH 贝克曼研究所 (BRICOH) 的项目 2 将研究提高针对 HIV 的抗病毒 RNA 表达的稳定性。 BRICOH 的项目 3 致力于改进逆转录病毒和慢病毒载体的比较研究。 在项目4中，临床试验中心将完成两项实验性自体干细胞移植（SCT）的比较试验，其中CD34+外周血祖细胞（PBPC）用编码针对TAT和REV的双锤头核酶的逆转录病毒转导。一项研究针对患有非霍奇金淋巴瘤的艾滋病患者，采用了一种消融性骨髓调理方案，另一项针对健康的 HIV-1 感染者，将使用羟基脲进行部分骨髓细胞减灭术。基础科学和实验室项目由三个核心领域支持。行政中心将监督基础科学和临床研究的管理。 DNA/RNA 分析实验室将评估移植后的骨髓和血液标本中核酶转基因的存在及其表达的稳定性。病毒学实验室将为 HIV 分析和新型抗 HIV RNA 的抗病毒作用评估提供支持。