Abstract
The production of therapeutic antibodies using mammalian cells remains a high-priority in the biopharmaceutical manufacturing industry. Bioengineers have targeted different cellular processes, including transcription, translation, secretion and post-translational modifications, to overcome the metabolic bottlenecks limiting production capacity and create high-producing mammalian cell lines. The polycomb group (PcG) proteins belong to a family of chromatin regulators with important roles in multicellular development. By overexpressing and screening genes from the PcG family, we have identified an epigenetic key player for biopharmaceutical manufacturing enhancement: the transcription factor Yin Yang 1 (YY1). The overexpression of YY1 led to an increase in the production of several product genes (SEAP, VEGF165, IgG including Rituximab), provided that human YY1 (hYY1) was expressed in human cells (HeLa, HT-1080, HEK-293T, FreeStyle™ 293-F) and Chinese hamster ovary cell-derived YY1 (cYY1) was expressed in CHO cells (CHO-K1, CHO-easyC, FreeStyle™ CHO-S, CHO-B13-24, CHO-IgG1). Ectopic expression of cYY1 in the stable CHO-derived IgG producer cell lines CHO-B13-24 and CHO-IgG1 increased the antibody titer up to 6-fold, suggesting that epigenetic engineering of mammalian production cell lines could become a new strategy to improve the manufacturing of complex protein pharmaceuticals.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
