Abstract
A critical avenue for the improvement of production of biotherapeutics in mammalian cells is to increase the stability of clonal cell lines. This study investigates the molecular basis for the onset of clonal heterogeneity in different recombinant protein (h-IgG) secreting CHO clones by characterizing specific mechanisms of transgene silencing, such as genetic drift, epigenetic modifications, and biochemical pathway perturbations. Using the Cell Xpress™ software module on the LEAP (Laser-Enabled Analysis and Processing) instrument platform, we assessed the relative levels of heterogeneity, as determined by specific cell productivity, in clonal CHO recombinant cell lines. Subpopulations of specific clones were generated by isolating cells from the highest 25% of secretors based on Cell Xpress™ data. These populations were analyzed via transcriptional profiling, copy number analysis, and epigenetic characterization to identify defining properties of cells that maintain or lose short-term production stability.
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Gerber, M.A., Lacy, K.A., Cresswell, J., Lin, N., Kayser, K.J., Caple, M.V. (2010). Cell Xpress™-Assisted Analysis of Clone Stability in Recombinant Chinese Hamster Ovary Cells. In: Noll, T. (eds) Cells and Culture. ESACT Proceedings, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3419-9_7
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DOI: https://doi.org/10.1007/978-90-481-3419-9_7
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Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-3418-2
Online ISBN: 978-90-481-3419-9
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