mRNA-Enhanced Cell Therapy and Cardiovascular Regeneration

Abstract

mRNA has emerged as an important biomolecule in the global call for the development of therapies during the COVID-19 pandemic. Synthetic in vitro-transcribed (IVT) mRNA can be engineered to mimic naturally occurring mRNA and can be used as a tool to target “undruggable” diseases. Recent advancement in the field of RNA therapeutics have addressed the challenges inherent to this drug molecule and this approach is now being applied to several therapeutic modalities, from cancer immunotherapy to vaccine development. In this review, we discussed the use of mRNA for stem cell generation or enhancement for the purpose of cardiovascular regeneration.

mRNA – A game changer in regenerative medicine, cell-based therapy and reprogramming strategies

“…Although emerging integration-free approaches, such as Sendai virus [215] , episomal [216] or plasmid DNA [217] and cell permeant proteins [218] minimized risks of genome insertion, cell reprogramming using these tools appeared insufficient [219] . Here, mRNA offers an exceptional benefit of transient and efficient protein expression with tight control over dosing, stoichiometry and time course while posing no risks of genome intrusion.…”

New Applications of Lipid and Polymer-Based Nanoparticles for Nucleic Acids Delivery

“…Clinical trials have investigated ASOs for lowering low-density lipoprotein cholesterol (LDL-C) [39], lowering transthyretin (TTR) blood levels [40][41][42], reducing atrial fibrillation burden [43], reducing serum lipoprotein (a) levels [44], and preventing neovascular glaucoma [45]. mRNA has also been evaluated for cardiovascular conditions, with several LNP-based formulations being tested for enhancing cardiac function and regeneration [46], reducing LDL-C levels [47], and treating endotheliopathy associated with vascular senescence [48,49]. Similarly, siRNA lipid-based formulations have been clinically tested for TTR-mediated amyloidosis [50] and hypercholesterolemia [51].…”

Electrically controlled mRNA delivery using a polypyrrole-graphene oxide hybrid film to promote osteogenic differentiation of human mesenchymal stem cells

“…However, despite its instability, delivery of messenger ribonucleic acid (mRNA) to target cells or tissues has attracted increasing attention because it can directly and quickly initiate protein synthesis and further affect various post-transcription processes [3][4][5]. Because of its high level of potential as a therapeutic agent, mRNA delivery in combination with biocompatible micro-and nano-sized carriers has been reported for various purposes, including viral vaccination, intracellular antigen synthesis, genome editing, immune cell modulation, and cellular conversion [6,7].…”