Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Science and Technology Department, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Int J Mol Sci. 2023 Mar 1;24(5):4737. doi: 10.3390/ijms24054737.
Myocardial infarction (MI) is a severe disease with high mortality worldwide. However, regenerative approaches remain limited and with poor efficacy. The major difficulty during MI is the substantial loss of cardiomyocytes (CMs) with limited capacity to regenerate. As a result, for decades, researchers have been engaged in developing useful therapies for myocardial regeneration. Gene therapy is an emerging approach for promoting myocardial regeneration. Modified mRNA (modRNA) is a highly potential delivery vector for gene transfer with its properties of efficiency, non-immunogenicity, transiency, and relative safety. Here, we discuss the optimization of modRNA-based therapy, including gene modification and delivery vectors of modRNA. Moreover, the effective of modRNA in animal MI treatment is also discussed. We conclude that modRNA-based therapy with appropriate therapeutical genes can potentially treat MI by directly promoting proliferation and differentiation, inhibiting apoptosis of CMs, as well as enhancing paracrine effects in terms of promoting angiogenesis and inhibiting fibrosis in heart milieu. Finally, we summarize the current challenges of modRNA-based cardiac treatment and look forward to the future direction of such treatment for MI. Further advanced clinical trials incorporating more MI patients should be conducted in order for modRNA therapy to become practical and feasible in real-world treatment.
心肌梗死（MI）是一种全球性的严重疾病，死亡率很高。然而，再生方法仍然有限，疗效也不佳。MI 的主要困难是心肌细胞（CMs）大量丢失，再生能力有限。因此，几十年来，研究人员一直在致力于开发用于心肌再生的有用疗法。基因治疗是促进心肌再生的一种新兴方法。修饰的 mRNA（modRNA）是一种具有高效性、非免疫原性、短暂性和相对安全性的高度有前途的基因传递载体。在这里，我们讨论了基于 modRNA 的治疗的优化，包括基因修饰和 modRNA 的递送载体。此外，还讨论了 modRNA 在动物 MI 治疗中的作用。我们得出结论，基于 modRNA 的治疗与适当的治疗基因相结合，可以通过直接促进 CM 的增殖和分化、抑制细胞凋亡，以及增强心脏环境中的血管生成和抑制纤维化的旁分泌作用，从而有潜力治疗 MI。最后，我们总结了基于 modRNA 的心脏治疗的当前挑战，并展望了这种治疗 MI 的未来方向。为了使 modRNA 治疗在实际治疗中变得实用和可行，应该在更多的 MI 患者中进行更先进的临床试验。
