In Vitro Investigations on Optimizing and Nebulization of IVT-mRNA Formulations for Potential Pulmonary-Based Alpha-1-Antitrypsin Deficiency Treatment

In vitro-transcribed (IVT) mRNA has come into focus in recent years as a potential therapeutic approach for the treatment of genetic diseases. The nebulized formulations IVT-mRNA-encoding alpha-1-antitrypsin (A1AT-mRNA) would be highly acceptable and tolerable remedy protein replacement therapy deficiency future. Here we show that lipoplexes containing A1AT-mRNA prepared optimum conditions could successfully transfect human bronchial epithelial cells without significant toxicity. A reduction transfection efficiency was observed aerosolized can partially overcome by increasing initial number components. A1AT produced from transfected is functional inhibit enzyme activity trypsin well elastase. Our data indicate aerosolization constitutes potentially powerful means to airway with purpose producing A1AT, while bringing along unique advantages IVT-mRNA.