Translational Molecular Pathology, MD Anderson Cancer Center, Texas State University, Houston, TX, USA.
Medical Biochemistry Department, Medical Research Division - Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences - National Research Centre, Cairo, Egypt.
Nat Rev Drug Discov. 2021 Aug;20(8):629-651. doi: 10.1038/s41573-021-00219-z. Epub 2021 Jun 18.
Therapeutic targeting of noncoding RNAs (ncRNAs), such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), represents an attractive approach for the treatment of cancers, as well as many other diseases. Over the past decade, substantial effort has been made towards the clinical application of RNA-based therapeutics, employing mostly antisense oligonucleotides and small interfering RNAs, with several gaining FDA approval. However, trial results have so far been ambivalent, with some studies reporting potent effects whereas others demonstrated limited efficacy or toxicity. Alternative entities such as antimiRNAs are undergoing clinical testing, and lncRNA-based therapeutics are gaining interest. In this Perspective, we discuss key challenges facing ncRNA therapeutics - including issues associated with specificity, delivery and tolerability - and focus on promising emerging approaches that aim to boost their success.
治疗性靶向非编码 RNA（ncRNAs），如 microRNAs（miRNAs）和长非编码 RNA（lncRNAs），是治疗癌症以及许多其他疾病的一种有吸引力的方法。在过去的十年中，人们在 RNA 治疗的临床应用方面做出了大量努力，主要采用反义寡核苷酸和小干扰 RNA，其中一些已获得 FDA 批准。然而，迄今为止，试验结果喜忧参半，一些研究报告了有效的作用，而另一些则显示出有限的疗效或毒性。正在进行临床试验的替代实体，如 antimiRNAs，以及基于 lncRNA 的治疗方法也引起了人们的兴趣。在本观点中，我们讨论了 ncRNA 治疗所面临的关键挑战 - 包括与特异性、递药和耐受性相关的问题 - 并重点介绍了旨在提高其成功率的有前途的新兴方法。
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