Virome Screening for Next Generation Nucleic Acid Delivery Vectors to the Lung

Delivering gene editing RNA drugs to specific organs such as the lung is difficult because RNA is unstable and most drug delivery vehicles encapsulating RNA go to the liver. We will look for viruses that naturally de-target the liver and target the lung. We will then hijack the envelope proteins from these viruses as new ways to deliver RNA. Towards this goal, we have developed a novel screening platform to find novel envelope proteins from diverse viruses with beneficial properties for delivery. This platform enables pooled screening based on each viral vector carrying a unique nucleic acid barcode that can be read out using sequencing. We will apply this platform and utilize the best envelope proteins to make non-replicating viral like particles (VLPs) that deliver RNA encoding gene editing drugs to the lung. We will individually validate the top three VLP in mice using Luciferase reporters and assess their targeting to the lung relative to the liver. We will also further improve the top VLP by introducing microRNA binding sites to the cargo such that the cargo will not be expressed in the liver. We hope that these novel delivery vectors will enable the development of genetic medicines for lung diseases such as Cystic Fibrosis