Screens for determining the cellular interactions of successful mRNA delivery systems.

Nucleic acid therapeutics are widely regarded as a breakthrough in medicine, but the main barrier to their successful application, other than for vaccination, is the small number of cells that take up and use the nucleic acid, typically only 1%. To treat genetic diseases or cancer, a much larger percentage of cells need to be transfected. Despite advances, it is still unclear why some cells in an apparently homogenous tissue are receptive while others are not. Here, the student will develop methods to determine difference between the interactions of different transfection reagents with cells to elucidate the relationship between transfection efficiency and the chemistry of lipid RNA carrier systems. They will use high throughput screens that determine the endogenous RNA expressed in cells that have been transfected as well as use a haploid genetic screen to determine what genes promote or prevent successful transfection for each carrier. The student will learn how to culture cells, genetically manipulate them, do FACS and antibiotic selection, isolate RNA for high throughput sequencing and do bioinformatics analysis. The project will lead to one or more methods that can be widely used to characterise nucleic acid delivery systems as well as lead to insights in the mechanisms of action of the specific formulations tested. It is therefore likely to have a major influence on the future of nucleic acid therapeutics.