Modified mRNA (modRNA) therapeutics are an innovative pharmaceutical technology with the capacity to create new types of drugs that will make personalized medicine possible. In the early 1990’s, mRNA was used to increase protein in the skeletal muscle and brain; however, two fundamental barriers prevent mRNA therapeutics from moving forward into clinical use. One barrier is that mRNA elicits an innate immune response, and the second barrier is that ribonucleases (RNases) in the body rapidly degrade mRNA rapidly. To overcome these barriers, two researchers, Katalin Karikó, PhD and Drew Weissman, MD demonstrated that replacing uridine (U) with naturally occurring pseudouridine (Ψ) attenuates the innate immune response and improves modRNA stability. Recently, modRNA has been successfully used to deliver SARS-COV-2 Spike protein and vaccinate millions of people around the world during the COVID-19 pandemic.

Despite the efforts of modern medicine and the progress in surgical management, myocardial infarction (MI) remains a major public health issue that often leads to adverse ventricular remodeling, heart failure (HF), and sometimes death. Our team uses modRNA technology to identify novel therapeutic targets that can benefit the heart after ischemic injury. In 2013, Zangi et al. pioneered using modRNA to treat heart disease by delivering beneficial VEGF-A modRNA at the time of MI. In the last seven years, we and others have shown that modified mRNA can temporarily change non-regenerative gene expression in the heart to allow brief regenerative capacity immediately post injury and to promote cardiac protection, vascularization, and regeneration following ischemia.