ABSTRACT
This chapter focuses on the biochemical properties; clinical use, pharmacological aspects, and production of recombinant human deoxyribonuclease (rhDNase) I. Deoxyribonucleases (DNases) are phosphodiesterases that catalyze the hydrolysis of deoxyribonucleic acid (DNA). The three-dimensional X-ray crystallographic structure of rhDNase I is very similar to the bovine form of DNase I. DNase I shows a strong preference for double-stranded DNA, and it degrades DNA in the presence of divalent cations by introducing single-stranded nicks through hydrolysis of P–O'3-bonds. Extremely sensitive DNase I assays have been developed using fluorescent DNA and fluorescent probes. RhDNase I can be used in conjunction with standard cystic fibrosis (CF) therapies, but it should not be used in patients with known hypersensitivity to rhDNase I and Chinese hamster ovary products. A gradual deamidation of rhDNase I also occur during storage in vials and am the major cause of its short shelf life. Different, well-designed clinical trials have demonstrated the effectiveness of rhDNase I in CF patients.
