Selective cleavage and measurement of mucin with proteases: treatment and diagnostic.

Abstract

Airway epithelial mucus is a key component of pathogen clearance and immune response as mucin complexes entrap irritants within the mucus hydrogel and expel them through coughing. For mucus to successfully function, it requires a proper ratio of mucins MUC5AC and MUC5B within the hydrogel complex to form the ideal viscosity. The underlying pathology of asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis include significant overexpression of MUC5AC, causing highly viscous airway mucus and interfering with disease clearance and respiration. We explore the application of designed proteases to selectively cleave MUC5AC and restore the healthy mucin ratio in MUC5AC upregulated samples. Furthermore, we are investigating a protease-substrate complex that triggers the release of a fluorescent molecule as cleavage occurs as a possible diagnostic tool to measure concentrations of MUC5AC across samples.