This is a continuation of the previous project (FFC#9/2018), in which the research team studied several DNases encoded by the human genome to find alternatives to the mucolytic drugs used in the treatment of pulmonary symptoms in CF patients. DNases are enzymes that selectively cut the DNA present in high quantities in the mucus. In fact, the components of the mucus include the so-called neutrophil extracellular traps or NETs which are structures that the human immune system creates in response to viral, bacterial and fungal infections. NETs are made up of proteins and other extracellular components and their main structural component is made up of DNA strands. Therefore, human DNases can be used as mucolytic agents in the therapy of lung disease. The project aims to perform the preclinical characterization of a new DNase. A new recombinant human DNase will be generated, in native and genetically modified form. The DNAse binding with polyethylene glycol (PEG) for greater in vivo activity and it will be investigated. In addition, its in vitro and ex vivo characterization by means of cell cultures and the patient’s sputum will be performed. The project should provide new insights into the management of CF inflammation through the destruction of extracellular DNA fibers and then develop innovative treatments for the reduction of inflammatory disease in CF patients.