Efficient, controlled delivery of synthetic anion carriers to epithelial cells for CFTR replacement therapy

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The genetic disease cystic fibrosis (CF) is caused by pathogenic variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The large number of variants and their complex effects on CFTR expression and function as an epithelial anion channel have stimulated the development of channel replacement therapeutic strategies for CF. In previous work, Professors AP Davis and DN Sheppard (University of Bristol) designed, synthesized and tested artificial anion transporters (anionophores) in artificial lipid membranes and cells. This work identified trans-decalin anionophores with promising biological activity, including potency and persistence without toxic effects. However, many anionophores with high activity in artificial lipid membranes are poorly deliverable to cells, arguing that they require specific drug delivery systems to achieve their therapeutic potential. This PhD project investigates the delivery of anionophores to epithelial cells using nanostructured drug-delivery platforms based on mesoporous silica particles developed by Dr AE Garcia-Bennett (Macquarie University). This innovative drug-delivery platform for anionophore delivery to CF epithelial cells will facilitate the translation of anionophores as a channel replacement therapy for CF. Moreover, the project provides excellent training in interdisciplinary research important for career development. It falls within the EPSRC Healthcare Technologies theme and Chemical biology and Biological Chemistry research area.