{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:56:26Z","timestamp":1789638986645,"version":"4.0.0"},"reference-count":73,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Cumulative evidence from several pre-clinical studies suggests that restoration of plasma DNase activity in a thrombo-inflammatory state may improve clinical outcomes. Following injury, hyperactivated immune cells release large amounts of granular proteins together with DNA, which often accumulate in the surrounding environment in so-called neutrophil extracellular traps (NETs). Degradation of excess NETs by systemic DNase administration offers a promising therapeutic approach to ameliorate inflammation and dissolve intravascular clots. In order to expand the therapeutic utility of human DNase I, a variant of the enzyme was developed that has both a prolonged systemic half-life and a higher catalytic activity compared to Dornase alfa (Pulmozyme\u00ae), the recombinant form of DNase I approved for inhaled therapy of cystic fibrosis. The hyperactive enzyme was \u201cPASylated\u201d by genetic fusion with a strongly hydrophilic and biodegradable PAS-polypeptide to increase its hydrodynamic volume and retard kidney filtration. A stable TurboCell\u2122 CHO-K1-based cell line was generated which is suitable for the future production of PASylated DNase I according to good manufacturing practice (GMP). Furthermore, a robust bioprocess strategy was devised and an effective downstream process was developed. The final protein product is characterized by excellent purity, favorable physicochemical properties, a 14-fold higher DNA-degrading activity than Dornase alfa and a sustained pharmacokinetic profile, with a 22-fold slower clearance in rats.<\/jats:p>","DOI":"10.3390\/pharmaceutics16070967","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T06:11:36Z","timestamp":1721887896000},"page":"967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Development of a Clonal and High-Yield Mammalian Cell Line for the Manufacturing of a Hyperactive Human DNase I with Extended Plasma Half-Life Using PASylation\u00ae Technology"],"prefix":"10.3390","volume":"16","author":[{"given":"Serge M.","family":"Stamm","sequence":"first","affiliation":[{"name":"Rentschler Biopharma SE, Erwin-Rentschler-Str. 21, 88471 Laupheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2319-3699","authenticated-orcid":false,"given":"Roland","family":"Wagner","sequence":"additional","affiliation":[{"name":"Rentschler Biopharma SE, Erwin-Rentschler-Str. 21, 88471 Laupheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietmar A.","family":"Lang","sequence":"additional","affiliation":[{"name":"Rentschler Biopharma SE, Erwin-Rentschler-Str. 21, 88471 Laupheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5717-498X","authenticated-orcid":false,"given":"Arne","family":"Skerra","sequence":"additional","affiliation":[{"name":"XL-Protein GmbH, Lise-Meitner-Str. 30, 85354 Freising, Germany"},{"name":"Lehrstuhl f\u00fcr Biologische Chemie, Technische Universit\u00e4t M\u00fcnchen, Emil-Erlenmeyer-Forum 5, 85354 Freising, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Gebauer","sequence":"additional","affiliation":[{"name":"XL-Protein GmbH, Lise-Meitner-Str. 30, 85354 Freising, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/j.yexcr.2011.02.013","article-title":"Introduction to current and future protein therapeutics: A protein engineering perspective","volume":"317","author":"Carter","year":"2011","journal-title":"Exp. 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