title: Deletion of a telomeric region on chromosome 8 correlates with higher productivity and stability of CHO cell lines.
abstract: Chinese Hamster Ovary (CHO) cells are widely used for large scale production of recombinant biopharmaceuticals. Although these cells have been extensively used, a demand to further increase the performance, for example, to facilitate the process of clone selection to isolate the highest producing cell lines that maintain stability of production over time is still existing. We compared gene expression profiles of high versus low producing CHO clones to identify regulated genes which can be used as biomarkers during clone selection or for cell line engineering. We present evidence that increased production rates and cell line stability are correlated with the loss of the telomeric region of the chromosome 8. A new parental CHO cell line lacking this region was generated and its capability for protein production was assessed. The average volumetric productivity of cells after gene transfer and selection was found to be several fold improved, facilitating the supply of early drug substance material to determine for example, quality. In addition, significantly more cell clones with a higher average productivity and higher protein production stability were obtained with the new host cell line after single cell cloning. This allows reduced efforts in single cell sorting, screening of fewer clones and raises the opportunity to circumvent time and labor-intensive stability studies.
authors.affiliation: Novartis Institutes for BioMedical Research, Basel, Switzerland. anett.ritter@novartis.com.|Novartis Pharma AG, Integrated Biologics Profiling Unit, Werk Klybeck Postfach CH-4002, Basel, Switzerland. anett.ritter@novartis.com.
authors.forename: Anett
authors.initials: A
authors.lastname: Ritter
authors.affiliation: Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Bernd
authors.initials: B
authors.lastname: Voedisch
authors.affiliation: Molecular Cytogenetics, Chrombios, Nussdorf, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Wienberg
authors.affiliation: Novartis Pharma AG, Integrated Biologics Profiling Unit, Werk Klybeck Postfach CH-4002, Basel, Switzerland.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Wilms
authors.affiliation: Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Sabine
authors.initials: S
authors.lastname: Geisse
authors.affiliation: Novartis Pharma AG, Integrated Biologics Profiling Unit, Werk Klybeck Postfach CH-4002, Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jostock
authors.affiliation: Novartis Pharma AG, Integrated Biologics Profiling Unit, Werk Klybeck Postfach CH-4002, Basel, Switzerland. holger.laux@novartis.com.
authors.forename: Holger
authors.initials: H
authors.lastname: Laux
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics; D016466:CHO Cells / Q000166:cytology / Q000378:metabolism*; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D015536:Down-Regulation; D005786:Gene Expression Regulation; D005818:Genetic Engineering / Q000379:methods; D006801:Humans; D011994:Recombinant Proteins / Q000235:genetics; D016615:Telomere / Q000235:genetics*; D059467:Transcriptome; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins
keywords: Chinese hamster ovary cells; cell line engineering; chromosomal deletion; productivity; recombinant gene expression; stability