RNA interference-based therapeutics for human immunodeficiency virus HIV-1 treatment: synthetic siRNA or vector-based shRNA?
RNA interference-based therapeutics for human immunodeficiency virus HIV-1 treatment: synthetic siRNA or vector-based shRNA?
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DOI：
10.1517/14712590903448158
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发表时间：
2010-02
影响因子：
4.6
通讯作者：
Shankar P
中科院分区：
文献类型：
--
作者：
Subramanya S;Kim SS;Manjunath N;Shankar P
尽管HAART具有非凡的临床益处，但终身抗逆转录病毒治疗方案的前景带来了重大的实际问题，这激发了人们对开发治疗HIV感染和消除持续病毒储库的新药和策略的兴趣。RNAi是一种非常有效的天然基因沉默机制，已成为HIV的新治疗可能性。我们的目的是讨论最近在克服将瞬时和稳定的RNAi使能技术转化为HIV感染临床应用的障碍方面的进展，综述涵盖了过去2-3年的文献。HIV抑制可以通过转染化学或酶促合成的siRNA或通过基于DNA的载体系统表达短发夹RNA（shRNA）来实现，短发夹RNA在细胞内加工成siRNA。本综述比较了这两种方法的优点和缺点，重点是技术和安全性问题，这将指导临床使用的适当策略的选择。将合成的siRNA引入细胞或使用载体驱动的shRNA稳定内源性地产生siRNA都已显示出在体外和在某些情况下在体内有效地抑制HIV复制。每种方法都有其自身的优点和局限性，如易于传递、沉默持续时间、逃逸突变体的出现和潜在毒性。因此，这两种方法似乎都有潜力作为未来的艾滋病毒治疗方法，一旦技术和安全问题的独特的每一种方法被克服。
Despite the extraordinary clinical benefits of HAART, the prospect of life-long antiretroviral regimen poses significant practical problems, which has spurred an interest in developing new drugs and strategies to treat HIV infection and to eliminate persistent viral reservoirs. RNAi is a highly potent natural gene silencing mechanism that has emerged as a novel therapeutic possibility for HIV. Our aim is to discuss the recent progress in overcoming the hurdles for translating transient and stable RNAi enabling technologies towards clinical applications in HIV infection and the review covers literature from the past 2–3 years. HIV inhibition can be achieved by transfection of chemically or enzymatically synthesized siRNAs or by DNA-based vector systems to express short hairpin RNAs (shRNAs) that are processed intracellularly into siRNA. This review compares the merits and shortcomings of the two approaches, focusing on technical and safety issues that will guide the choice of the appropriate strategy for clinical use. Introduction of synthetic siRNA into cells or its stable endogenous production using vector-driven shRNA have both been shown to effectively suppress HIV replication in vitro and in some instances in vivo. Each method has its own advantages and limitations in terms of ease of delivery, duration of silencing, emergence of escape mutants and potential toxicity. Thus, both methods appear to have potential as future therapeutics for HIV, once the technical and safety issues unique to each of the approaches are overcome.
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