Researchers from BeOne Medicines (formerly BeiGene) have demonstrated that overexpressing the cytoplasmic poly(A)-binding protein gene Pabpc1 can enhance protein titers in Chinese hamster ovary (CHO) cell lines by 30–50%. This finding, detailed in a recent publication, shows consistent results across various antibody formats, including multispecific and monoclonal antibodies.
This advancement opens avenues for biomanufacturers to develop practical screening strategies aimed at identifying factors that could further enhance expression levels or optimize specific product attributes in CHO cells. While the applicability of this approach to other cell lines, such as HEK293 or PER.C6, remains untested, the implications for CHO cell productivity are significant.
The Pabpc1 gene plays a critical role in mRNA stability and translation, extending the half-life of target mRNAs. The research team noted that prior studies had not explored the impact of Pabpc1 overexpression on recombinant protein production in CHO cells. Their work indicates that overexpressing Pabpc1 in low-expression clones resulted in substantial gains in productivity, particularly for bispecific antibodies, which saw a 50% increase.
Moreover, the study revealed that Pabpc1 overexpression could positively influence cellular metabolism, leading to reduced accumulation of lactic acid and ammonia, thereby fostering a more conducive environment for protein production. The interaction between Pabpc1 and eukaryotic initiation factor 4E (eIF4E) was also identified as a mechanism that enhances translation initiation efficiency.
While the precise mechanisms by which Pabpc1 enhances recombinant protein productivity in CHO cells are still being investigated, the findings suggest a novel and effective strategy with substantial potential for industrial application. The research team intends to refine this approach and explore its broader applicability in biopharmaceutical manufacturing.
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