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Effective and efficient characterization of Chinese hamster ovary production cell lines using automated intracellular staining and statistical modeling

机译:使用自动化细胞内染色和统计建模的中国仓鼠卵巢生产细胞系有效和高效地表征

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摘要

Mammalian cell line development is critical to bioproduct manufacturing. Success requires selecting a line with desirable performance characteristics, including consistent expression throughout the proposed manufacturing window. Given the genetic and phenotypic flux inherent to immortalized lines such as Chinese hamster ovary cells, clonally-derived cell line characterization is vital. We describe here the development and implementation of a novel addition to our characterization approach to ensure production cell line suitability: automated intracellular staining with statistical modeling. Case studies are presented which highlight this method's sensitivity to epigenetic expression effects, closing a gap left by our historically-leveraged genetic suitability characterization. Additionally, we demonstrate how an orthogonal, complimentary assay can help identify opportunities for improvement in even a well-established methodology such as our genetic suitability assessment. (c) 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:570-583, 2018
机译:哺乳动物细胞系发育对生物中文化制造至关重要。成功需要选择具有所需性能特征的线,包括在整个建议的制造窗口中的一致表达。鉴于遗传和表型通量固有的永生化线,如中国仓鼠卵巢细胞,克隆衍生的细胞系表征是至关重要的。我们在这里描述了一种新颖的对我们的表征方法的开发和实施,以确保生产细胞系适用性:用统计建模自动化细胞内染色。提出了案例研究,突出了这种方法对表述表达效应的敏感性,通过我们历史杠杆释放的遗传适应性表征留下的差距。此外,我们展示了正交,互补的测定如何有助于确定甚至既有良好的方法,例如诸如遗传适用性评估的良好方法。 (c)2018美国化学工程师学院Biotechnol。 Prog。,34:570-583,2018

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