mRNA therapy for myocardial infarction: A review of targets and delivery vehicles

Abstract

Cardiovascular diseases are the leading cause of death in the world. This is partly due to the low regenerative capacity of adult hearts. mRNA therapy is a promising approach under development for cardiac diseases. In mRNA therapy, expression of the target protein is modulated by delivering synthetic mRNA. mRNA therapy benefits cardiac regeneration by increasing cardiomyocyte proliferation, reducing fibrosis, and promoting angiogenesis. Because mRNA is translated in the cytoplasm, the delivery efficiency of mRNA into the cytoplasm and nucleus significantly affects its therapeutic efficacy. To improve delivery efficiency, non-viral vehicles such as lipid nanoparticles have been developed. Non-viral vehicles can protect mRNA from enzymatic degradation and facilitate the cellular internalization of mRNA. In addition to non-viral vehicles, viral vectors have been designed to deliver mRNA templates into cardiac cells. This article reviews lipid nanoparticles, polymer nanoparticles, and viral vectors that have been utilized to deliver mRNA into the heart. Because of the growing interest in lipid nanoparticles, recent advances in lipid nanoparticles designed for cardiac mRNA delivery are discussed. Besides, potential targets of mRNA therapy for myocardial infarction are discussed. Gene therapies that have been investigated in patients with cardiac diseases are analyzed. Reviewing mRNA therapy from a clinically relevant perspective can reveal needs for future investigations.

Hydrogels for the Treatment of Myocardial Infarction: Design and Therapeutic Strategies

“…Gene therapy can use DNA, plasmids, messenger RNA (mRNA), small interfering RNA (siRNA), or microRNA (miRNA). [ 169 ] When these genes are taken up by cells in the vicinity of damaged heart tissue, cells can use these genes to produce therapeutic proteins that promote tissue repair, angiogenesis, and reduce excessive inflammation. [ 170 ] However, effective vectors are needed to deliver genes to the damaged heart muscle, and hydrogels can provide targeted and continuous gene delivery to the damaged tissue, or hydrogels can be injected directly into the infarct area for in situ gelation to enhance therapeutic effects.…”