Modified mRNA as a Therapeutic Tool for the Heart

Despite various clinical modalities available for patients, heart disease remains among the leading causes of mortality and morbidity worldwide. Genetic medicine, particularly mRNA, has broad potential as a therapeutic. More specifically, mRNA-based protein delivery has been used in the fields of cancer and vaccination, but recent changes to the structural composition of mRNA have led the scientific community to swiftly embrace it as a new drug to deliver missing genes to injured myocardium and many other organs. Modified mRNA (modRNA)–based gene delivery features transient but potent protein translation and low immunogenicity, with minimal risk of insertional mutagenesis. In this review, we compared and listed the advantages of modRNA over traditional vectors for cardiac therapy, with particular focus on using modRNA therapy in cardiac repair. We present a comprehensive overview of modRNA’s role in cardiomyocyte (CM) proliferation, cardiac vascularization, and prevention of cardiac apoptosis. We also emphasize recent advances in modRNA delivery strategies and discuss the challenges for its clinical translation.