RT Journal Article
SR Electronic
T1 Multi-omics profiling of CHO parental hosts reveals cell line-specific variations in bioprocessing traits
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 532150
DO 10.1101/532150
A1 Meiyappan Lakshmanan
A1 Yee Jiun Kok
A1 Alison P. Lee
A1 Sarantos Kyriakopoulos
A1 Hsueh Lee Lim
A1 Gavin Teo
A1 Swan Li Poh
A1 Wen Qin Tang
A1 Jongkwang Hong
A1 Andy Hee-Meng Tan
A1 Xuezhi Bi
A1 Ying Swan Ho
A1 Peiqing Zhang
A1 Say Kong Ng
A1 Dong-Yup Lee
YR 2019
UL http://biorxiv.org/content/early/2019/01/31/532150.abstract
AB 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 have 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 analysis 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.