Lauren Feeney, Veronica Carvalhal, X. Christopher Yu, Betty Chan, David A. Michels, Yajun Jennifer Wang, Amy Shen, Jan Ressl, Brendon Dusel and Michael W. Laird Eliminating tyrosine sequence variants in CHO cell lines producing recombinant monoclonal antibodies Biotechnology and Bioengineering 110
This work investigates a commonly observed sequence variant (SV) in several CHO cell produced monoclonal antibodies, and how the levels of key amino acids in the cell culture fermentation process can impact the level of SV. Specifically, several tyrosine residues throughout the protein were found to have either phenylalanine or histidine incorporated in place of tyrosine; it was determined that this event strongly correlated with tyrosine depletion. The data suggests that the mechanism of sequence variant formation is mRNA mistranslation.
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