An inducible system for protein production in CHO cells

Production of biopharmaceuticals is a rapidly growing industry with a need for advanced production platforms. There is a demand for CHO-derived clones that express high levels of recombinant protein in a stable fashion. We have developed an inducible system for expression in CHO cells, and have optimized various stages in the workflow from cDNA to large-scale production. An inducible system allows us to use a biphasic protocol for production, wherein protein expression is kept “OFF” during the growth phase and only turned “ON” for production. We hypothesize that this allows us to isolate clones expressing high levels of protein that may not be otherwise tolerated when expressed in a constitutive manner. Even so, high-expressors are rare and therefore large numbers of clones need to be screened to identify potential candidates. Although automation has allowed us to increase our throughput, clone selection is still time-consuming and labour-intensive, making it imperative to implement a strategy that is predictive of success during the later stages of scale-up and production. With the help of various case studies, this presentation will discuss the advantages and disadvantages of various small-scale models and illustrate how elements of our scale-up strategy can be incorporated early in the workflow.