Stenvang Jan, Petri Andreas, Lindow Morten, Obad Susanna, Kauppinen Sakari
Santaris Pharma, Kogle Allé 6, DK-2970 Hørsholm, Denmark.
Silence. 2012 Jan 9;3(1):1. doi: 10.1186/1758-907X-3-1.
MicroRNAs (miRNAs) have emerged as important post-transcriptional regulators of gene expression in many developmental and cellular processes. Moreover, there is now ample evidence that perturbations in the levels of individual or entire families of miRNAs are strongly associated with the pathogenesis of a wide range of human diseases. Indeed, disease-associated miRNAs represent a new class of targets for the development of miRNA-based therapeutic modalities, which may yield patient benefits unobtainable by other therapeutic approaches. The recent explosion in miRNA research has accelerated the development of several computational and experimental approaches for probing miRNA functions in cell culture and in vivo. In this review, we focus on the use of antisense oligonucleotides (antimiRs) in miRNA inhibition for loss-of-function studies. We provide an overview of the currently employed antisense chemistries and their utility in designing antimiR oligonucleotides. Furthermore, we describe the most commonly used in vivo delivery strategies and discuss different approaches for assessment of miRNA inhibition and potential off-target effects. Finally, we summarize recent progress in antimiR mediated pharmacological inhibition of disease-associated miRNAs, which shows great promise in the development of novel miRNA-based therapeutics.
微小RNA（miRNA）已成为许多发育和细胞过程中基因表达的重要转录后调节因子。此外，现在有充分的证据表明，单个或整个miRNA家族水平的扰动与多种人类疾病的发病机制密切相关。事实上，与疾病相关的miRNA代表了一类新的基于miRNA的治疗方式开发靶点，这可能带来其他治疗方法无法实现的患者受益。最近miRNA研究的爆发加速了几种用于在细胞培养和体内探究miRNA功能的计算和实验方法的发展。在本综述中，我们重点关注反义寡核苷酸（抗miR）在miRNA抑制中的应用，用于功能缺失研究。我们概述了目前使用的反义化学及其在设计抗miR寡核苷酸中的效用。此外，我们描述了最常用的体内递送策略，并讨论了评估miRNA抑制和潜在脱靶效应的不同方法。最后，我们总结了抗miR介导的对疾病相关miRNA的药理学抑制的最新进展，这在新型基于miRNA的治疗方法开发中显示出巨大潜力。
