Metabolic engineering can resolve CHO cell protein processing and secretion bottlenecks.
Geneva, Switzerland (PRWEB) March 05, 2013
Selexis SA, a global life sciences company for drug discovery, cell line development and scale-up to manufacturing of therapeutic proteins, announced today that the results from Company’s internal drug discovery platform R&D program have been published in Metabolic Engineering(1).
“CHO cell engineering to prevent polypeptide aggregation and improve therapeutic protein secretion”
The ability to efficiently produce recombinant proteins in a secreted form is highly desirable and cultured mammalian cells such as CHO cells have become the preferred host as they secrete proteins with human-like post-translational modifications. However, attempts to express high levels of particular proteins in CHO cells may consistently result in low yields, even for non-engineered proteins such as immunoglobulins. In this study, we identified the responsible faulty step at the stage of translational arrest, translocation and early processing for such a ‘‘difficult-to-express’’ immunoglobulin, resulting in improper cleavage of the light chain and its precipitation in an insoluble cellular fraction unable to contribute to immunoglobulin assembly. We further show that proper processing and secretion were restored by over-expressing human signal receptor protein SRP14 and other components of the secretion pathway. This allowed the expression of the difficult-to-express protein to high yields, and it also increased the production of an easy-to-express protein. Our results demonstrate that components of the secretory and processing pathways can be limiting, and that engineering of the secretory pathway may be used to improve the secretion efficiency of therapeutic proteins from CHO cells.
(1) The full article can be found online at http://www.sciencedirect.com/science/article/pii/S1096717613000025
About Selexis SA
Headquartered in Geneva, Switzerland, Selexis SA is a global life science company with innovative technologies and world-class expert services for drug discovery, cell line development and scale-up to manufacturing of therapeutic proteins. The Company’s SUREtechnology Platform™ is based on Selexis Genetic Elements™ — novel DNA-based elements that control the dynamic organization of chromatin within all mammalian cells and allow for higher and morestable expression of recombinant proteins.
Selexis has generated over 1,700 cell lines being used in a variety of programs from drug discovery to late-stage clinical trials.
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