Combinatorial anti-HIV gene therapy: using a multipronged approach to reach beyond HAART.
Combinatorial anti-HIV gene therapy: using a multipronged approach to reach beyond HAART.
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“柏林病人”在没有抗逆转录病毒治疗的情况下保持抑制的艾滋病毒血症水平，仍然是艾滋病毒根除研究的旗手。然而，围绕他的功能性治愈的独特情况并不适用于大多数HIV+患者。为了在全世界更多的感染个体中实现功能性或杀菌性治愈，针对病毒生命周期的多个阶段的组合治疗将是必不可少的。最近已经探索了几种抗HIV基因治疗方法，包括破坏CD 4 + T细胞和CD 34+造血干细胞中的CCR 5和CXCR 4辅助受体基因座。然而，对这些策略在患者和更相关的HIV模型系统（如非人灵长类动物）中的疗效知之甚少。组合方法，包括整合前病毒的遗传破坏，内源性限制因子的功能增强，和/或使用药理学佐剂，可以放大CCR 5/CXCR 4基因破坏的抗HIV作用。重要的是，将基因破坏分子递送到感兴趣的遗传位点可能需要在逐个细胞类型的基础上进行优化。在这篇综述中，我们强调了最有前途的基因治疗方法来对抗HIV感染，将这些治疗方法提供给造血细胞的方法，并强调需要靶向病毒复制前和后进入，以安装一个适当的强大的防御传播感染。
The “Berlin Patient,” who maintains suppressed levels of HIV viremia in the absence of antiretroviral therapy, continues to be a standard bearer in HIV eradication research. However, the unique circumstances surrounding his functional cure are not applicable to most HIV+ patients. To achieve a functional or sterilizing cure in a greater number of infected individuals worldwide, combinatorial treatments, targeting multiple stages of the viral life cycle, will be essential. Several anti-HIV gene therapy approaches have recently been explored, including disruption of the CCR5 and CXCR4 coreceptor loci in CD4+ T-cells and CD34+ hematopoietic stem cells. However, less is known about the efficacy of these strategies in patients and more relevant HIV model systems such as nonhuman primates. Combinatorial approaches, including genetic disruption of integrated provirus, functional enhancement of endogenous restriction factors, and/or the use of pharmacological adjuvants, could amplify the anti-HIV effects of CCR5/CXCR4 gene disruption. Importantly, delivering gene disruption molecules to genetic sites of interest will likely require optimization on a cell type-by-cell type basis. In this review, we highlight the most promising gene therapy approaches to combat HIV infection, methods to deliver these therapies to hematopoietic cells, and emphasize the need to target viral replication pre- and post-entry in order to mount a suitably robust defense against spreading infection.
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影响因子：
4.6
作者：
Arrildt, Kathryn Twigg;Joseph, Sarah Beth;Swanstrom, Ronald
通讯作者：
Swanstrom, Ronald
影响因子：
12.8
作者：
Edling, AE;Choksi, S;Korngold, R
通讯作者：
Korngold, R
影响因子：
5.2
作者：
Cossarini, Francesca;Galli, Andrea;Nozza, Silvia
通讯作者：
Nozza, Silvia
影响因子：
4.9
作者：
Duong, Yen T.;Meadows, D. Christopher;North, Thomas W.
通讯作者：
North, Thomas W.
DOI：
10.3390/v4020309
发表时间：
2012-02
期刊：
Viruses
影响因子：
--
作者：
Didigu CA;Doms RW
通讯作者：
Doms RW