用于心血管疾病和再生的细胞特异性 mRNA 疗法

Raj Kishore, Ajit Magadum
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摘要

心血管疾病(CVDs)是全球重大的健康负担,需要创新的治疗方法。近年来,mRNA 疗法已成为有效防治心血管疾病的一种前景广阔的策略。与传统的小分子药物不同,mRNA 疗法通过向靶细胞输送特定的 mRNA 分子来直接调节细胞功能。这种方法具有前所未有的优势,包括能够利用内源性细胞机制合成蛋白质,从而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 疗法在心血管疾病方面的潜力现状。首先,它概述了与传统心血管疾病治疗方法相关的挑战,并强调了对靶向疗法的需求。随后,它阐明了 mRNA 疗法的基本原理和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在改善向心脏细胞、活化成纤维细胞和其他相关细胞类型定向递送 mRNA 方面已显示出前景。此外,综述还强调了细胞特异性 mRNA 疗法在治疗动脉粥样硬化、心肌梗塞、心力衰竭和心律失常等心血管疾病各方面的不同应用。通过调节涉及心肌细胞增殖、炎症、血管生成、组织修复和细胞存活的关键调控基因,mRNA 疗法有望在心血管疾病发病的多个阶段进行干预。尽管细胞特异性 mRNA 疗法具有巨大的潜力,但本摘要也指出了将其从临床前研究转化为临床应用所面临的挑战,例如脱靶效应和递送。总之,细胞特异性 mRNA 疗法已成为治疗心血管疾病的革命性基因疗法,它提供的靶向干预有可能显著改善患者的预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cell-Specific mRNA Therapeutics for Cardiovascular Diseases and Regeneration
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.
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