Abstract 17202: Synthetic Modified RNA Driven Delivery of Insulin-Like Growth Factor-1 Promotes Early Cardiomyocyte Survival Post-Acute Myocardial Infarction

To extend the temporal window for cytoprotection in cardiomyocytes undergoing apoptosis after hypoxia and myocardial infarction (MI), a synthetic modified RNA (modRNA) was used to drive delivery of insulin-like growth factor-1 (IGF1) within the area at risk in a murine model of MI. Transient transfection of synthetic GFP modRNA as an tracking indicator, with polyethylenimine (PEI)-based nanoparticle, showed efficient delivery of modRNA derived protein and minimum cytotoxicity in HL-1 cardiomyocytes (CM; 44±5%). ModRNA-IGF1 protein expression and secreted levels increased 3.5 fold (p<0.05) at 24 hours and peaked at 48 hours post-transfection. The expression efficiency of modRNA was further enhanced (~2 fold at 24 hours post-transfection; p<0.05) under hypoxia-induced apoptosis conditions. ModRNA augmented secreted and cell associated IGF1 promoting CM survival and abrogating cell apoptosis (71±5% in controls to 37±7%, p<0.05). Translation of modRNA-IGF1 was sufficient to induce downstream increases in Akt ...