Swan C H, Torbett B E
Department of Molecular, The Scripps Research Institute, La Jolla, CA 92037, USA.
J Med Primatol. 2006 Aug;35(4-5):236-47. doi: 10.1111/j.1600-0684.2006.00172.x.
Research efforts to prevent viral entry by developing small molecule inhibitors against HIV-1 chemokine coreceptors have yielded promising clinical results. However, resistance to some chemokine receptor inhibitors has been recently documented, and therefore, alternative methods of HIV-1 coreceptor disruption are needed.
We will describe current HIV-1 vector-delivered genetic disruption mechanisms that target HIV-1 chemokine coreceptors, such as RNA interference, ribozymes, zinc fingers, intrakines, and intrabodies, and frame the use of these gene delivery chemokine receptor disruption mechanisms in the context of current small molecule blocker/antagonists of CCR5 and CXCR4. In addition, we will discuss the importance of evaluating HIV-1 vector-delivered viral entry prevention mechanisms in the rhesus macaque SIV non-human primate model in regard to pathogenesis and therapeutic efficacy.
通过研发针对HIV-1趋化因子共受体的小分子抑制剂来预防病毒进入的研究工作已取得了令人鼓舞的临床结果。然而，最近有文献记载了对某些趋化因子受体抑制剂的耐药性，因此，需要有替代的HIV-1共受体破坏方法。
我们将描述当前通过HIV-1载体传递的针对HIV-1趋化因子共受体的基因破坏机制，如RNA干扰、核酶、锌指、细胞内趋化因子和细胞内抗体，并结合当前CCR5和CXCR4的小分子阻滞剂/拮抗剂来阐述这些基因传递趋化因子受体破坏机制的应用。此外，我们将讨论在恒河猴SIV非人类灵长类动物模型中评估HIV-1载体传递的病毒进入预防机制对于发病机制和治疗效果的重要性。
