Multi‐omics profiling of CHO parental hosts reveals cell line‐specific variations in bioprocessing traits
Autor: | Wen Qin Tang, Peiqing Zhang, Jong Kwang Hong, Gavin Teo, Dong-Yup Lee, Hsueh Lee Lim, Sarantos Kyriakopoulos, Ying Swan Ho, Yee Jiun Kok, Xuezhi Bi, Meiyappan Lakshmanan, Andy Hee-Meng Tan, Say Kong Ng, Alison P. Lee, Swan Li Poh |
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Rok vydání: | 2019 |
Předmět: |
0106 biological sciences
0301 basic medicine Glycosylation Proteome Bioengineering CHO Cells Biology 01 natural sciences Applied Microbiology and Biotechnology law.invention Transcriptome 03 medical and health sciences Cricetulus law 010608 biotechnology Animals Bioprocess Genetic heterogeneity Chinese hamster ovary cell Transfection Phenotype Recombinant Proteins Cell biology 030104 developmental biology Cell culture Recombinant DNA Biotechnology |
Zdroj: | Biotechnology and Bioengineering. 116:2117-2129 |
ISSN: | 1097-0290 0006-3592 |
Popis: | Chinese hamster ovary (CHO) cells are the most prevalent mammalian cell factories for producing recombinant therapeutic proteins due to their ability to synthesize human-like post-translational modifications and ease of maintenance in suspension cultures. Currently, a wide variety of CHO host cell lines has been developed; substantial differences exist in their phenotypes even when transfected with the same target vector. However, relatively less is known about the influence of their inherited genetic heterogeneity on phenotypic traits and production potential from the bioprocessing point of view. Herein, we present a global transcriptome and proteome profiling of three commonly used parental cell lines (CHO-K1, CHO-DXB11, and CHO-DG44) in suspension cultures and further report their growth-related characteristics, and N- and O-glycosylation patterns of host cell proteins (HCPs). The comparative multi-omics and subsequent genome-scale metabolic network model-based enrichment analyses indicated that some physiological variations of CHO cells grown in the same media are possibly originated from the genetic deficits, particularly in the cell-cycle progression. Moreover, the dihydrofolate reductase deficient DG44 and DXB11 possess relatively less active metabolism when compared to K1 cells. The protein processing abilities and the N- and O-glycosylation profiles also differ significantly across the host cell lines, suggesting the need to select host cells in a rational manner for the cell line development on the basis of recombinant protein being produced. |
Databáze: | OpenAIRE |
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