Synthetic MicroRNAs Stimulate Cardiac Repair
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MicroRNAs (miRNA) are short noncoding double-stranded RNAs that were found in several life forms, such as viruses, plants, animals, and humans. Their main function is to regulate gene translation by post-transcriptional binding of the RNA and prevent ribosomal translation (RNA silencing).1,2 miRNAs are important for the regulation of many biological processes in our body, including organ development, maintaining stable, and steady-state function of tissues during adulthood and after injury or disease.1,2 Although several miRNAs were found to be beneficial for cardiac regeneration, miRNAs are currently not in clinical use.3–5 In 2012, Dr. Mauro Giacca Laboratory showed that human miRNAs can induce neonatal cardiomyocyte proliferation.6 They identified 40 miRNAs that significantly increased both DNA synthesis and cytokinesis in neonatal mouse and rat cardiomyocytes. They then selected two of these miRNAs (hsa-miR-590 and hsa-miR-199a) and showed their ability to promote adult cardiomyocytes cell cycle re-entry in vivo. In addition, they showed that in a mouse myocardial infarction (MI) model, delivery of adeno-associated vectors (AAV) encoding hsa-miR-590 or hsa-miR-199a induced cardiac regeneration with almost complete recovery of cardiac functional parameters. Although viral-derived vectors such as AAV could be efficient …