Herrera-Carrillo Elena, Berkhout Ben
Laboratory of Experimental Virology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, the Netherlands.
Nucleic Acids Res. 2017 Oct 13;45(18):10369-10379. doi: 10.1093/nar/gkx779.
MicroRNAs (miRNAs) play a pivotal role in the regulation of cellular gene expression via the conserved RNA interference (RNAi) mechanism. Biogenesis of the unusual miR-451 does not require Dicer. This molecule is instead processed by the Argonaute 2 (Ago2) enzyme. Similarly, unconventional short hairpin RNA (shRNA) molecules have been designed as miR-451 mimics that rely exclusively on Ago2 for maturation. We will review recent progress made in the understanding of this alternative processing route. Next, we describe different Dicer-independent shRNA designs that have been developed and discuss their therapeutic advantages and disadvantages. As an example, we will present the route towards development of a durable gene therapy against HIV-1.
微小RNA（miRNA）通过保守的RNA干扰（RNAi）机制在细胞基因表达调控中发挥关键作用。不同寻常的miR-451的生物合成不需要Dicer。相反，该分子由Argonaute 2（Ago2）酶加工。同样，非传统短发夹RNA（shRNA）分子已被设计为仅依赖Ago2进行成熟的miR-451模拟物。我们将综述在理解这一替代加工途径方面取得的最新进展。接下来，我们描述已开发的不同的不依赖Dicer的shRNA设计，并讨论它们的治疗优缺点。作为一个例子，我们将展示针对HIV-1的持久基因治疗的开发途径。
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