ANTI-HIV RNA TRANSDUCTION INTO BLOOD STEM CELLS IN AIDS

来自City of Hope国家医学中心（COH）的这个综合临床前/临床项目提出了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，旨在改善基因转移，基因表达，以及使用逆转录病毒和慢病毒载体抑制艾滋病毒。洛杉矶儿童医院的项目1将评估人造血干细胞转导后改进的载体在单核细胞和T细胞中的表达。Beckman Research Institute of COH（BRICOH）的项目2将研究针对HIV的抗病毒RNA表达的稳定性。BRICOH的项目3致力于改进的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比较性试验，即用编码靶向达特和REV的双锤头状核酶的逆转录病毒转导CD 34+外周血祖细胞（PBPC）进行实验性自体干细胞移植（SCT）。一项研究在患有非霍奇金淋巴瘤的艾滋病患者中进行，采用消融性骨髓预处理方案，另一项研究在健康的HIV-1感染者中进行，将使用羟基脲进行部分骨髓细胞减少。基础科学和实验室计划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分析实验室将评价移植后骨髓和血液标本中核酶转基因表达的存在和稳定性。病毒学实验室将为艾滋病毒分析和新的抗艾滋病毒RNA的抗病毒效果评估提供支持。

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.