Figure

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Schematic representation of double-stranded DNA. DNase I can generate single-chain nicks in both DNA strands at the indicated phosphate-oxygen bonds. The obtained oligonucleotides, which are at least two nucleotides long, bear a 5'-phosphate and a 3'-hydroxyl termini.

pancreas. This drastically intensified the biochemical investigations on and with DNase I. In 1950, Armstrong, et al., reported that partially purified bovine pancreatic DNase I reduced the viscosity of purulent cystic fibrosis (CF) lung secretions [8]. Clinical trials with inhaled bovine DNase I followed soon after and showed clinical improvements in CF patients and patients with purulent secretions [9-11]. In 1958, bovine pancreatic DNase I (Dornavac) was approved in the United States as a mucolytic agent for human use [12]. However, in the early 1960s, severe adverse reactions like bronchospasms and asthmatic attacks led to the withdrawal of bovine pancreatic DNase I from the market [13,14]. During the following decades, clinical interest in DNase I diminished, but DNase I received much attention once again when Shak, et al. [12] cloned the human version of it in 1990. In 1993, this led to the marketing of recombinant human (rh) DNase I under the trade name Pulmozyme® (Genentech Inc., San Francisco, CA) for use in CF patients. In this chapter, we will focus on the biochemical properties, clinical use, pharmacological aspects, and production of rhDNase I.

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