Kishore Raj, Magadum Ajit
Department of Cardiovascular Sciences, Temple University, Philadelphia, PA 19140, USA.
J Cardiovasc Dev Dis. 2024 Jan 26;11(2):38. doi: 10.3390/jcdd11020038.
Cardiovascular diseases (CVDs) represent a significant global health burden, demanding innovative therapeutic approaches. In recent years, mRNA therapeutics have emerged as a promising strategy to combat CVDs effectively. Unlike conventional small-molecule drugs, mRNA therapeutics enable the direct modulation of cellular functions by delivering specific mRNA molecules to target cells. This approach offers unprecedented advantages, including the ability to harness endogenous cellular machinery for protein synthesis, thus allowing precise control over gene expression without insertion into the genome. This review summarizes the current status of the potential of cell-specific mRNA therapeutics in the context of cardiovascular diseases. First, it outlines the challenges associated with traditional CVD treatments and emphasizes the need for targeted therapies. Subsequently, it elucidates the underlying principles of mRNA therapeutics and the development of advanced delivery systems to ensure cell-specificity and enhanced efficacy. Notably, innovative delivery methods such as lipid nanoparticles and exosomes have shown promise in improving the targeted delivery of mRNA to cardiac cells, activated fibroblasts, and other relevant cell types. Furthermore, the review highlights the diverse applications of cell-specific mRNA therapeutics in addressing various aspects of cardiovascular diseases, including atherosclerosis, myocardial infarction, heart failure, and arrhythmias. By modulating key regulatory genes involved in cardiomyocyte proliferation, inflammation, angiogenesis, tissue repair, and cell survival, mRNA therapeutics hold the potential to intervene at multiple stages of CVD pathogenesis. Despite its immense potential, this abstract acknowledges the challenges in translating cell-specific mRNA therapeutics from preclinical studies to clinical applications like off-target effects and delivery. In conclusion, cell-specific mRNA therapeutics have emerged as a revolutionary gene therapy approach for CVD, offering targeted interventions with the potential to significantly improve patient outcomes.
心血管疾病(CVDs)是一项重大的全球健康负担,需要创新的治疗方法。近年来,mRNA疗法已成为有效对抗心血管疾病的一种有前景的策略。与传统小分子药物不同,mRNA疗法通过将特定的mRNA分子递送至靶细胞来直接调节细胞功能。这种方法具有前所未有的优势,包括利用内源性细胞机制进行蛋白质合成的能力,从而能够在不插入基因组的情况下精确控制基因表达。本综述总结了细胞特异性mRNA疗法在心血管疾病背景下的潜在应用现状。首先,概述了传统心血管疾病治疗方法所面临的挑战,并强调了靶向治疗的必要性。随后,阐明了mRNA疗法的基本原理以及先进递送系统的开发,以确保细胞特异性和增强疗效。值得注意的是,脂质纳米颗粒和外泌体等创新递送方法已显示出有望改善mRNA向心脏细胞、活化成纤维细胞和其他相关细胞类型的靶向递送。此外,该综述强调了细胞特异性mRNA疗法在解决心血管疾病各个方面的多样化应用,包括动脉粥样硬化、心肌梗死、心力衰竭和心律失常。通过调节参与心肌细胞增殖、炎症、血管生成、组织修复和细胞存活的关键调控基因,mRNA疗法有可能在心血管疾病发病机制的多个阶段进行干预。尽管具有巨大潜力,但本摘要也承认将细胞特异性mRNA疗法从临床前研究转化为临床应用时存在挑战,如脱靶效应和递送问题。总之,细胞特异性mRNA疗法已成为心血管疾病的一种革命性基因治疗方法,提供靶向干预措施,有可能显著改善患者预后。