Department of Medical Microbiology, Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Prog Mol Biol Transl Sci. 2011;102:141-63. doi: 10.1016/B978-0-12-415795-8.00001-5.
RNA interference (RNAi) is a cellular mechanism that mediates sequence-specific gene silencing at the posttranscriptional level. RNAi can be used as an antiviral approach against human pathogens. An attractive target for RNAi therapeutics is the human immunodeficiency virus type 1 (HIV-1), and the first clinical trial using a lentiviral gene therapy was initiated in early 2008. In this chapter, we focus on some basic principles of such an RNAi-based gene therapy against HIV-1. This includes the subjects of target site selection within the viral RNA genome, the phenomenon of viral escape, and therapeutic strategies to prevent viral escape. The latter antiescape strategies include diverse combinatorial RNAi approaches that are all directed against the HIV-1 RNA genome. As an alternative strategy, we also discuss the possibilities and restrictions of targeting cellular cofactors that are essential for virus replication, but less important for cell physiology.
RNA 干扰 (RNAi) 是一种细胞机制，可在转录后水平介导序列特异性基因沉默。RNAi 可用作针对人类病原体的抗病毒方法。RNAi 治疗的一个有吸引力的靶标是人类免疫缺陷病毒 1 型 (HIV-1)，并于 2008 年初启动了首个使用慢病毒基因治疗的临床试验。在本章中，我们重点介绍了基于 RNAi 的针对 HIV-1 的基因治疗的一些基本原则。这包括在病毒 RNA 基因组内选择靶位点、病毒逃逸现象以及预防病毒逃逸的治疗策略。后者的抗逃逸策略包括针对 HIV-1 RNA 基因组的各种组合 RNAi 方法。作为替代策略，我们还讨论了针对对病毒复制至关重要但对细胞生理学不太重要的细胞辅助因子的可能性和限制。
