Department of Physiology and Cell Biology, Reno School of Medicine, University of Nevada, 1664 North Virginia Street, Reno, NV 89557, USA.
Int J Mol Sci. 2022 Mar 1;23(5):2736. doi: 10.3390/ijms23052736.
Following the discovery of nucleic acids by Friedrich Miescher in 1868, DNA and RNA were recognized as the genetic code containing the necessary information for proper cell functioning. In the years following these discoveries, vast knowledge of the seemingly endless roles of RNA have become better understood. Additionally, many new types of RNAs were discovered that seemed to have no coding properties (non-coding RNAs), such as microRNAs (miRNAs). The discovery of these new RNAs created a new avenue for treating various human diseases. However, RNA is relatively unstable and is degraded fairly rapidly once administered; this has led to the development of novel delivery mechanisms, such as nanoparticles to increase stability as well as to prevent off-target effects of these molecules. Current advances in RNA-based therapies have substantial promise in treating and preventing many human diseases and disorders through fixing the pathology instead of merely treating the symptomology similarly to traditional therapeutics. Although many RNA therapeutics have made it to clinical trials, only a few have been FDA approved thus far. Additionally, the results of clinical trials for RNA therapeutics have been ambivalent to date, with some studies demonstrating potent efficacy, whereas others have limited effectiveness and/or toxicity. Momentum is building in the clinic for RNA therapeutics; future clinical care of human diseases will likely comprise promising RNA therapeutics. This review focuses on the current advances of RNA therapeutics and addresses current challenges with their development.
继 Friedrich Miescher 于 1868 年发现核酸之后，DNA 和 RNA 被认为是包含适当细胞功能所需信息的遗传密码。在这些发现之后的几年里，人们对 RNA 看似无穷无尽的作用有了更深入的了解。此外，还发现了许多似乎没有编码特性的新型 RNA（非编码 RNA），如 microRNAs（miRNAs）。这些新 RNA 的发现为治疗各种人类疾病开辟了新途径。然而，RNA 相对不稳定，一旦给药就会迅速降解；这导致了新型递送机制的发展，如纳米颗粒，以提高稳定性并防止这些分子的脱靶效应。基于 RNA 的治疗方法的最新进展有望通过修复病理学来治疗和预防许多人类疾病和障碍，而不仅仅是像传统疗法那样治疗症状。尽管许多 RNA 疗法已进入临床试验，但迄今为止只有少数获得 FDA 批准。此外，RNA 疗法的临床试验结果迄今为止一直存在矛盾，一些研究显示出强大的疗效，而其他研究则疗效有限和/或毒性。RNA 疗法在临床上的势头正在增强；未来对人类疾病的临床治疗可能包括有前途的 RNA 疗法。本综述重点介绍了 RNA 疗法的最新进展，并讨论了其开发面临的当前挑战。
