DNase Human

DNase I cleaves DNA preferentially at phosphodiester linkages adjacent to a pyrimidine nucleotide, yielding 5’-phosphate-terminated polynucleotides with a free hydroxyl group on position 3’ . It acts on single-stranded DNA, double-stranded DNA, and chromatin . The enzyme is synthesized as a precursor and contains a 22-residue signal sequence that is cleaved upon secretion, resulting in the 260-residue mature enzyme . DNase I is secreted by the pancreas and parotid glands, consistent with its proposed primary role of digesting nucleic acids in the gastrointestinal tract . However, it is also present in blood, urine, and other tissues, suggesting additional functions .

Recombinant human DNase I (rhDNase I), also known as dornase alfa or Pulmozyme®, has been expressed in mammalian cell culture, specifically in Chinese hamster ovary cells . This recombinant form has been developed clinically and is aerosolized into the airways for the treatment of pulmonary diseases, particularly in patients with cystic fibrosis .

In cystic fibrosis, the thick and sticky mucus in the airways contains high molecular weight DNA from the breakdown of neutrophils. This DNA contributes to the viscosity and elasticity of the mucus, making it difficult to clear from the airways. rhDNase I hydrolyzes the DNA in the purulent sputum of cystic fibrosis patients, reducing the sputum’s viscoelasticity . By breaking down the DNA into smaller fragments, rhDNase I reduces mucus viscosity and improves mucus clearability, enhancing pulmonary function and reducing recurrent exacerbations of respiratory symptoms .

rhDNase I was approved for clinical use in 1993 and has been widely used as a safe and effective therapy for cystic fibrosis patients . The use of rhDNase I has also been investigated in other diseases where exogenous DNA has been implicated in the disease pathology .