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Resurrection of an anti-inflammatory therapy through protein engineering

30 months
Approved budget:
Assistant Professor Lyn Wise
Professor Roslyn Kemp
Associate Professor Joel Tyndall
Professor Michelle Glass
Health issue:
Inflammatory and immune system
Proposal type:
Explorer Grant
Lay summary
Inflammatory diseases represent a huge global burden, but the medicines we have to treat them are limited. Advances in steroids, anti-metabolites, and monoclonal antibodies have offered improved treatment specificity, but are associated with severe side-effects. Cytokines that control immune responses have shown great therapeutic potential, but their pleiotropic actions can make them difficult, and risky, to use. Here, we propose to take a cytokine therapy that failed in human trails, and turn it into a potent, yet safe, anti-inflammatory agent. Specifically, we aim to bias this cytokine’s action towards therapeutic pathways, and away from harmful ones. We intend to achieve this through protein engineering, by altering how the cytokine interacts with, and induces signalling from, its receptor complex. The anti-inflammatory agent produced will likely be useful in a range of human diseases, and the knowledge and tools generated could change how cytokine therapies are developed.