靶向 HIV 和 HIV 核心受体 CCR5 的 microRNA 样双功能 siRNA 的合理设计。
Rational design of micro-RNA-like bifunctional siRNAs targeting HIV and the HIV coreceptor CCR5.
机构信息
Department of Molecular Biology, Beckman Research Institute of City of Hope, Duarte, California, USA.
出版信息
Mol Ther. 2010 Apr;18(4):796-802. doi: 10.1038/mt.2009.321. Epub 2010 Jan 26.
Abstract
Small-interfering RNAs (siRNAs) and micro-RNAs (miRNAs) are distinguished by their modes of action. SiRNAs serve as guides for sequence-specific cleavage of complementary mRNAs and the targets can be in coding or noncoding regions of the target transcripts. MiRNAs inhibit translation via partially complementary base-pairing to 3' untranslated regions (UTRs) and are generally ineffective when targeting coding regions of a transcript. In this study, we deliberately designed siRNAs that simultaneously direct cleavage and translational suppression of HIV RNAs, or cleavage of the mRNA encoding the HIV coreceptor CCR5 and suppression of translation of HIV. These bifunctional siRNAs trigger inhibition of HIV infection and replication in cell culture. The design principles have wide applications throughout the genome, as about 90% of genes harbor sites that make the design of bifunctional siRNAs possible.
摘要
小干扰 RNA（siRNAs）和 microRNAs（miRNAs）的作用方式不同。siRNAs 作为序列特异性切割互补 mRNA 的向导，其靶标可以在靶转录本的编码或非编码区域。miRNAs 通过与 3'非翻译区（UTR）的部分互补碱基配对来抑制翻译，并且当靶向转录本的编码区域时通常无效。在这项研究中，我们故意设计了 siRNAs，这些 siRNAs 可以同时指导 HIV RNA 的切割和翻译抑制，或者编码 HIV 辅助受体 CCR5 的 mRNA 的切割和 HIV 翻译的抑制。这些双功能 siRNAs 可触发细胞培养中 HIV 感染和复制的抑制。这些设计原则在整个基因组中具有广泛的应用，因为大约 90%的基因都有可以设计双功能 siRNAs 的位点。
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