Journal article
Mitigating Clonal Variation in Recombinant Mammalian Cell Lines
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark1
Ajou University2
University of California at San Diego3
CHO Cell Line Engineering and Design, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark4
Korea Advanced Institute of Science and Technology5
Mammalian expression platforms are primary production systems for therapeutic proteins that require complex post-translational modifications. Current processes used for developing recombinant mammalian cell lines generate clonal cell lines with high phenotypic heterogeneity, which has puzzled researchers that use mammalian cell culture systems for a long time.
Advances in mammalian genome-editing technologies and systems biotechnology have shed light on clonal variation and enabled rational cell engineering in a targeted manner. We propose a new approach for a next-generation cell line development platform that can minimize clonal variation. Combined with the knowledge-based selection of ideal integration sites and engineering targets, targeted integration-based cell line development will allow tailored control of recombinant gene expression with predicted phenotypes.
Language: | English |
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Year: | 2019 |
Pages: | 931-942 |
ISSN: | 18793096 , 01677799 and 01679430 |
Types: | Journal article |
DOI: | 10.1016/j.tibtech.2019.02.007 |
ORCIDs: | Lee, Jae Seong and Kildegaard, Helene Faustrup |