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Mitigating Clonal Variation in Recombinant Mammalian Cell Lines.

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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… Click to show full abstract

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.

Keywords: cell lines; mammalian cell; clonal variation; cell; recombinant mammalian

Journal Title: Trends in biotechnology
Year Published: 2019

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