Human anti-HIV-1 tat sFv intrabodies for gene therapy of advanced HIV-1-infection and AIDS
Human anti-HIV-1 tat sFv intrabodies for gene therapy of advanced HIV-1-infection and AIDS
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DOI：
10.1016/s0022-1759(99)00159-3
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发表时间：
1999-12-10
影响因子：
2.2
通讯作者：
Winkler, A
中科院分区：
文献类型：
--
作者：
Marasco, WA;LaVecchio, J;Winkler, A
高效抗逆转录病毒疗法（HAART）治疗HIV-1感染和艾滋病的早期成功提出了一个问题，即基因疗法在治疗这种慢性传染病中是否有合法的作用。然而，在许多患者中，对病毒复制的深度抑制是短暂的，特别是如果患者过去曾接受过序贯单药治疗，感染了高度耐药的HIV-1分离株，或作为“假期”或由于药物不耐受而暂时停止治疗。此外，由于潜伏感染细胞的储库可持续数年，即使对检测不到病毒血症的应答患者也可能需要终身坚持维持HAART。通过将抗逆转录病毒“抗性”基因引入CD 4（+）T细胞的基因治疗是一种可以在体内对这些HIV-1易感细胞提供长期保护的方法。我们通过开发HIV-1复制所必需的关键HIV-1反式激活蛋白达特的胞内抗体来探索这种方法。这种挑衅性的治疗方法将在临床基因治疗试验中进行测试，为确定抗Tat胞内抗体基因治疗与HAART一起是否可以为晚期HIV-1感染患者的免疫重建提供治疗策略奠定基础。(C)1999 Elsevier Science B. V.保留所有权利。
The early successes of highly active anti-retroviral therapies (HAART) for the treatment of HIV-1-infection and AIDS have raised the question as to whether there is a legitimate role for gene therapy in the treatment of this chronic infectious disease. However, in many patients the profound suppression of viral replication is short lived, particularly if patients have been treated with sequential monotherapies in the past, have been infected with a highly drug resistant isolate of HIV-1, or have temporarily discontinued therapy as a "holiday" or because of drug intolerance. In addition, life-long adherence to maintenance HAART will probably be required even in responding patients with undetectable viremia because of the reservoirs of latently infected cells that can persist for years. Gene therapy through the introduction of anti-retroviral "resistance" genes into CD4(+) T cells is one approach that could give long term protection to these HIV-1 susceptible cells in vivo. We have explored this approach by developing intrabodies to the critical HIV-1 transactivator protein, Tat that is absolutely required for HIV-1 replication. This provocative treatment approach, that will be tested in a clinical gene therapy trial, sets the groundwork for determining if anti-Tat intrabody gene therapy together with HAART can provide a treatment strategy for the immune reconstitution of HIV-1-infected patients with advanced disease. (C) 1999 Elsevier Science B.V. All rights reserved.