title: The art of CHO cell engineering: A comprehensive retrospect and future perspectives.
abstract: Chinese hamster ovary (CHO) cells represent the most frequently applied host cell system for industrial manufacturing of recombinant protein therapeutics. CHO cells are capable of producing high quality biologics exhibiting human-like post-translational modifications in gram quantities. However, production processes for biopharmaceuticals using mammalian cells still suffer from cellular limitations such as limited growth, low productivity and stress resistance as well as higher expenses compared to bacterial or yeast based expression systems. Besides bioprocess, media and vector optimizations, advances in host cell engineering technologies comprising introduction, knock-out or post-transcriptional silencing of engineering genes have paved the way for remarkable achievements in CHO cell line development. Furthermore, thorough analysis of cellular pathways and mechanisms important for bioprocessing steadily unravels novel target molecules which might be addressed by functional genomic tools in order to establish superior production cell factories. This review provides a comprehensive summary of the most fundamental achievements in CHO cell engineering over the past three decades. Finally, the authors discuss the potential of novel and innovative methodologies that might contribute to further enhancement of existing CHO based production platforms for biopharmaceutical manufacturing in the future.
authors.affiliation: Institute of Applied Biotechnology, University of Applied Sciences Biberach, Hubertus-Liebrecht-Strasse 35, 88400 Biberach, Germany; University of Ulm, Faculty of Medicine, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Electronic address: simon.fischer@boehringer-ingelheim.com.
authors.forename: Simon
authors.initials: S
authors.lastname: Fischer
authors.affiliation: Institute of Applied Biotechnology, University of Applied Sciences Biberach, Hubertus-Liebrecht-Strasse 35, 88400 Biberach, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Handrick
authors.affiliation: Institute of Applied Biotechnology, University of Applied Sciences Biberach, Hubertus-Liebrecht-Strasse 35, 88400 Biberach, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Otte
mesh_terms: D000818:Animals; D016466:CHO Cells / Q000166:cytology / Q000378:metabolism*; D060846:Cell Engineering / Q000639:trends*; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D011994:Recombinant Proteins
keywords: Biopharmaceuticals; CRISPR; Cell engineering; Chinese hamster ovary (CHO); Gene knockout; Genome editing; TALEN; ZFN; microRNA; siRNA