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Review
. 2024 Jan-Dec:33:9636897241248956.
doi: 10.1177/09636897241248956.

Potential Application of Modified mRNA in Cardiac Regeneration

Aline Yen Ling Wang  1 , Yun-Ching Chang  2   3 , Kuan-Hung Chen  4   5 , Charles Yuen Yung Loh  6
Affiliations
Review

Potential Application of Modified mRNA in Cardiac Regeneration

Aline Yen Ling Wang et al. Cell Transplant. 2024 Jan-Dec.

Abstract

Heart failure remains the leading cause of human death worldwide. After a heart attack, the formation of scar tissue due to the massive death of cardiomyocytes leads to heart failure and sudden death in most cases. In addition, the regenerative ability of the adult heart is limited after injury, partly due to cell-cycle arrest in cardiomyocytes. In the current post-COVID-19 era, urgently authorized modified mRNA (modRNA) vaccines have been widely used to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, modRNA-based protein replacement may act as an alternative strategy for improving heart disease. It is a safe, effective, transient, low-immunogenic, and integration-free strategy for in vivo protein expression, in addition to recombinant protein and stem-cell regenerative therapies. In this review, we provide a summary of various cardiac factors that have been utilized with the modRNA method to enhance cardiovascular regeneration, cardiomyocyte proliferation, fibrosis inhibition, and apoptosis inhibition. We further discuss other cardiac factors, modRNA delivery methods, and injection methods using the modRNA approach to explore their application potential in heart disease. Factors for promoting cardiomyocyte proliferation such as a cocktail of three genes comprising FoxM1, Id1, and Jnk3-shRNA (FIJs), gp130, and melatonin have potential to be applied in the modRNA approach. We also discuss the current challenges with respect to modRNA-based cardiac regenerative medicine that need to be overcome to apply this approach to heart disease. This review provides a short description for investigators interested in the development of alternative cardiac regenerative medicines using the modRNA platform.

Keywords: cardiac regeneration; modRNA platform; modRNA-based protein replacement; modified mRNA; therapeutic targets.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Utilizing the modRNA platform for direct cardiac repair involves delivering target genes to induce cardiac proliferation, inhibit fibrosis and apoptosis, and promote cardiovascular regeneration, as presented in Table 2.
Figure 2.
Figure 2.
The prevention of heart disease involves utilizing the modRNA platform to target potential genes associated with cardiac proliferation, as outlined in Table 3.
See this image and copyright information in PMC

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