Institute of Laboratory Medicine, University Hospital, LMU Munich, Munich, Germany.
Thromb Haemost. 2019 Aug;119(8):1222-1236. doi: 10.1055/s-0039-1692680. Epub 2019 Jul 16.
Long noncoding ribonucleic acids (lncRNAs) have been defined as transcripts which are > 200 ribonucleotides in size and are not translated into protein. Recent work has shown that many lncRNAs do have specific molecular functions and biological effects, and are involved in a growing number of diseases, including atherosclerosis. As a consequence, lncRNAs are also becoming interesting targets for therapeutic intervention. Here, we focus on lncRNAs which are expressed in the arterial wall, and describe potential RNA therapeutic approaches of atherosclerosis by manipulating lncRNAs without affecting genome deoxyribonucleic acid content: Starting out with an overview of all lncRNAs that have so far been implicated in atherosclerosis by studies, we describe methodologies for their activation, inactivation, and RNA sequence manipulation. We continue by addressing how artificial (nonnative) therapeutic lncRNAs may be designed, and which molecular functions these designer lncRNAs may exploit. We conclude with an outlook on approaches for chemical lncRNA modification, RNA mass production, and site-specific therapeutic delivery.
长链非编码核糖核酸（lncRNA）被定义为长度大于 200 个核糖核苷酸的转录本，不能翻译成蛋白质。最近的研究表明，许多 lncRNA 确实具有特定的分子功能和生物学效应，并参与越来越多的疾病，包括动脉粥样硬化。因此，lncRNA 也成为治疗干预的有趣靶点。在这里，我们专注于在动脉壁中表达的 lncRNA，并通过操纵 lncRNA 而不影响基因组脱氧核糖核酸含量来描述动脉粥样硬化的潜在 RNA 治疗方法：首先概述迄今为止通过研究表明与动脉粥样硬化有关的所有 lncRNA，我们描述了激活、失活和 RNA 序列操作的方法。然后，我们讨论如何设计人工（非天然）治疗性 lncRNA，以及这些设计的 lncRNA 可以利用哪些分子功能。最后，我们展望了化学 lncRNA 修饰、RNA 大规模生产和靶向治疗递送的方法。
