Mandel Center for Hypertension and Atherosclerosis, and the Duke Cardiovascular Research Center, Duke University Medical Center, Durham, NC (V.J.D., C.P.H.).
National Academy of Medicine, Washington, DC (V.J.D.).
Circulation. 2024 Feb 27;149(9):707-716. doi: 10.1161/CIRCULATIONAHA.123.067373. Epub 2024 Feb 26.
RNA therapeutics hold significant promise in the treatment of cardiovascular diseases. RNAs are biologically diverse and functionally specific and can be used for gain- or loss-of-function purposes. The effectiveness of mRNA-based vaccines in the recent COVID-19 pandemic has undoubtedly proven the benefits of an RNA-based approach. RNA-based therapies are becoming more common as a treatment modality for cardiovascular disease. This is most evident in hypertension where several small interfering RNA-based drugs have proven to be effective in managing high blood pressure in several clinical trials. As befits a rapidly burgeoning field, there is significant interest in other classes of RNA. Revascularization of the infarcted heart through an mRNA drug is under clinical investigation. mRNA technology may provide the platform for the expression of paracrine factors for myocardial protection and regeneration. Emergent technologies on the basis of microRNAs and gene editing are tackling complex diseases in a novel fashion. RNA-based gene editing offers hope of permanent cures for monogenic cardiovascular diseases, and long-term control of complex diseases such as essential hypertension, as well. Likewise, microRNAs are proving effective in regenerating cardiac muscle. The aim of this review is to provide an overview of the current landscape of RNA-based therapies for the treatment of cardiovascular disease. The review describes the large number of RNA molecules that exist with a discussion of the clinical development of each RNA type. In addition, the review also presents a number of avenues for future development.
RNA 疗法在心血管疾病治疗中具有重要的应用前景。RNA 具有丰富的生物学多样性和功能特异性，可用于功能获得或功能丧失的目的。在最近的 COVID-19 大流行中，基于 mRNA 的疫苗的有效性无疑证明了基于 RNA 的方法的益处。基于 RNA 的疗法作为心血管疾病的治疗方式越来越常见。在高血压中最为明显，几种基于小干扰 RNA 的药物已被证明在几项临床试验中有效治疗高血压。作为一个迅速发展的领域，人们对其他类型的 RNA 也表现出极大的兴趣。通过 mRNA 药物对梗死心脏进行血运重建正在进行临床研究。mRNA 技术可能为心肌保护和再生的旁分泌因子的表达提供平台。基于 microRNA 和基因编辑的新兴技术正在以新颖的方式治疗复杂疾病。基于 RNA 的基因编辑为单基因心血管疾病的永久性治疗以及原发性高血压等复杂疾病的长期控制带来了希望。同样，microRNA 在心肌再生方面也被证明是有效的。本文旨在概述基于 RNA 的疗法治疗心血管疾病的最新进展。本文描述了大量存在的 RNA 分子，并讨论了每种 RNA 类型的临床开发情况。此外，本文还提出了一些未来的发展方向。
