A combined SANS-Neutron reflectivity study on RNA nanocomplexes formation and aerosolisation for pulmonary delivery_SANS

There is a growing interest in developing RNA therapeutics such as small interfering and messenger RNA o treat respiratory diseases. However, RNAs are notoriously unstable, rendering their delivery extremely challenging. Currently, RNA delivery is limited to parenteral administration with poor lung distribution. A safe and effective pulmonary delivery system that allows the direct application of RNA therapeutics to the site of action in the lung would be critical to extend the applications of RNA therapeutics to lung-related diseases. Furthermore, inhaled mRNA vaccine could improve efficacy against respiratory infections by triggering mucosal immune response in a non-invasive manner. Recently, our group has successfully developed a biomimetic PEGylated KL4 peptide (patent pending) which is demonstrated to be a safe and effective non-viral vector for RNA delivery to the lung. The overall aim of this study is to analyse the structural characteristics of the PEGylated KL4/ RNA nanocomplexes systematically using different size of RNAs, and to monitor the structural stability of the nanocomplexes during nebulisation. The outcomes of the study would provide valuable insights that allow us to optimise and tailor an inhalable/aerosolised PEGylated KL4 peptide based RNA delivery applicable for a wide range of RNA therapeutics.