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Recombinant Human Deoxyribonuclease I

Human deoxyribonuclease I (DNase I) is an endonuclease that catalyzes the hydrolysis of extracellular DNA and is just one of the numerous types of nucleases found in nature. The enzymatic mechanism for a single turnover is reasonably well understood based on biochemical and structural studies that a...

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Autores principales: Lazarus, Robert A., Wagener†, Jeffrey S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124075/
http://dx.doi.org/10.1007/978-3-030-00710-2_22
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author Lazarus, Robert A.
Wagener†, Jeffrey S.
author_facet Lazarus, Robert A.
Wagener†, Jeffrey S.
author_sort Lazarus, Robert A.
collection PubMed
description Human deoxyribonuclease I (DNase I) is an endonuclease that catalyzes the hydrolysis of extracellular DNA and is just one of the numerous types of nucleases found in nature. The enzymatic mechanism for a single turnover is reasonably well understood based on biochemical and structural studies that are consistent with divalent metal ion dependent nonspecific nicking of a phosphodiester bond in one of the strands of double stranded DNA. Recombinant human DNase I (rhDNase I, rhDNase, Pulmozyme(®), dornase alfa) has been expressed in mammalian cell culture in Chinese hamster ovary cells and developed clinically where it is aerosolized into the airways for treatment of pulmonary disease in patients with cystic fibrosis (CF). rhDNase I hydrolyzes the DNA in purulent sputum of CF patients and reduces sputum viscoelasticity. Reduction of high molecular weight DNA into smaller fragments by treatment with aerosolized rhDNase I has been proposed as the mechanism to reduce the mucus viscosity and improve mucus clearability from obstructed airways in patients. The improved clearance of the purulent mucus enhances pulmonary function and reduces 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 CF patients. The use of rhDNase I has also been investigated in other diseases where exogenous DNA has been implicated in the disease pathology.
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spelling pubmed-71240752020-04-06 Recombinant Human Deoxyribonuclease I Lazarus, Robert A. Wagener†, Jeffrey S. Pharmaceutical Biotechnology Article Human deoxyribonuclease I (DNase I) is an endonuclease that catalyzes the hydrolysis of extracellular DNA and is just one of the numerous types of nucleases found in nature. The enzymatic mechanism for a single turnover is reasonably well understood based on biochemical and structural studies that are consistent with divalent metal ion dependent nonspecific nicking of a phosphodiester bond in one of the strands of double stranded DNA. Recombinant human DNase I (rhDNase I, rhDNase, Pulmozyme(®), dornase alfa) has been expressed in mammalian cell culture in Chinese hamster ovary cells and developed clinically where it is aerosolized into the airways for treatment of pulmonary disease in patients with cystic fibrosis (CF). rhDNase I hydrolyzes the DNA in purulent sputum of CF patients and reduces sputum viscoelasticity. Reduction of high molecular weight DNA into smaller fragments by treatment with aerosolized rhDNase I has been proposed as the mechanism to reduce the mucus viscosity and improve mucus clearability from obstructed airways in patients. The improved clearance of the purulent mucus enhances pulmonary function and reduces 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 CF patients. The use of rhDNase I has also been investigated in other diseases where exogenous DNA has been implicated in the disease pathology. 2019-04-14 /pmc/articles/PMC7124075/ http://dx.doi.org/10.1007/978-3-030-00710-2_22 Text en © Springer Nature Switzerland AG 2019 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Article
Lazarus, Robert A.
Wagener†, Jeffrey S.
Recombinant Human Deoxyribonuclease I
title Recombinant Human Deoxyribonuclease I
title_full Recombinant Human Deoxyribonuclease I
title_fullStr Recombinant Human Deoxyribonuclease I
title_full_unstemmed Recombinant Human Deoxyribonuclease I
title_short Recombinant Human Deoxyribonuclease I
title_sort recombinant human deoxyribonuclease i
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7124075/
http://dx.doi.org/10.1007/978-3-030-00710-2_22
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