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Actin-Resistant DNase1L2 as a Potential Therapeutics for CF Lung Disease

Biomolecules. 2021-03; 
Danila Delfino, Giulia Mori, Claudio Rivetti, Antonella Grigoletto, Gloria Bizzotto, Cristian Cavozzi, Marco Malatesta, Davide Cavazzini, Gianfranco Pasut, Riccardo Percudani
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Bacterial Expression DNase1L2-S (ENST00000382437.8; Q92874-2) lacking the predicted signal peptide were cloned into E. coli expression vector pET29b (GenScript, Piscataway, NJ, USA). Get A Quote

摘要

In cystic fibrosis (CF), the accumulation of viscous lung secretions rich in DNA and actin is a major cause of chronic inflammation and recurrent infections leading to airway obstruction. Mucolytic therapy based on recombinant human DNase1 reduces CF mucus viscosity and promotes airway clearance. However, the marked susceptibility to actin inhibition of this enzyme prompts the research of alternative treatments that could overcome this limitation. Within the human DNase repertoire, DNase1L2 is ideally suited for this purpose because it exhibits metal-dependent endonuclease activity on plasmid DNA in a broad range of pH with acidic optimum and is minimally inhibited by actin. When tested on CF artificial mucus e... More

关键词

PEGylation, Pichia pastoris, cystic fibrosis, endonuclease, enzyme therapeutics, mucolytics