The approval of the first small interfering RNA (siRNA) drug Patisiran by FDA in 2018 marks a new era of RNA interference (RNAi) therapeutics. MicroRNAs (miRNA), an important post-transcriptional gene regulator, are also the subject of both basic research and clinical trials. Both siRNA and miRNA mimics are ~21 nucleotides RNA duplexes inducing mRNA silencing. Given the well performance of siRNA, researchers ask whether miRNA mimics are unnecessary or developed siRNA technology can pave the way for the emergence of miRNA mimic drugs. Through comprehensive comparison of siRNA and miRNA, we focus on (1) the common features and lessons learnt from the success of siRNAs; (2) the unique characteristics of miRNA that potentially offer additional therapeutic advantages and opportunities; (3) key areas of ongoing research that will contribute to clinical application of miRNA mimics. In conclusion, miRNA mimics have unique properties and advantages which cannot be fully matched by siRNA in clinical applications. MiRNAs are endogenous molecules and the gene silencing effects of miRNA mimics can be regulated or buffered to ameliorate or eliminate off-target effects. An in-depth understanding of the differences between siRNA and miRNA mimics will facilitate the development of miRNA mimic drugs.

中文翻译：

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RNA 衍生疗法的有效工具：siRNA 干扰或 miRNA 模拟。

2018年FDA批准第一个小干扰RNA（siRNA）药物Patisiran标志着RNA干扰（RNAi）治疗的新时代。微小RNA（miRNA）是一种重要的转录后基因调节因子，也是基础研究和临床试验的主题。siRNA 和 miRNA 模拟物都是约 21 个核苷酸的 RNA 双链体，可诱导 mRNA 沉默。鉴于 siRNA 的良好性能，研究人员询问是否不需要 miRNA 模拟物，或者开发的 siRNA 技术是否可以为 miRNA 模拟药物的出现铺平道路。通过对 siRNA 和 miRNA 的综合比较，我们重点关注 (1) siRNA 成功的共同特征和经验教训；(2) miRNA 的独特特征可能提供额外的治疗优势和机会；(3) 正在进行的研究的关键领域，这些领域将有助于 miRNA 模拟物的临床应用。总之，miRNA模拟物具有临床应用中siRNA无法完全匹配的独特性质和优势。miRNA 是内源性分子，可以调节或缓冲 miRNA 模拟物的基因沉默效应，以改善或消除脱靶效应。深入了解 siRNA 和 miRNA 模拟物之间的差异将促进 miRNA 模拟物药物的开发。