Episomal stable pools in WAVE bioreactors for fast and robust protein production



Recombinant proteins are important resources in several stages of drug discovery as well as many other types of research. The amounts of pure protein required span from a few micrograms for immunisations to hundreds of milligrams or even grams for activity evaluations and structure determinations. Here a highly scalable process for protein production in CHO cells that generates robust product quality and high performance throughout scales is presented.

Recurrent production of large amounts of protein is usually done by generating stable cell lines from high-producing clones. In drug discovery and other projects focusing on multiple targets this will become costly and time-consuming. In this study a highly scalable protein production platform that utilizes the same technology for transient expression and stable pools is presented. Transient expression is used for small-scale production and the QMCF technology from Icosagen is applied to large-scale recombinant protein production in WAVE bioreactors to generate episomal stable pools in suspension cell culture. This shortens timelines for production scaling since proliferation can be performed simultaneously as antibiotic selection. The large-scale episomal pool protocol was compared to the transient expression protocol in terms of production titers for six human secreted proteins. The results show a great improvement in purified protein/ml culture for most of the targets, while the rest showed similar amounts using both protocols.

The platform is shown to deliver a seamless and efficient scale-up with robust product quality, while keeping the flexibility in the development process, and could therefore be considered as a suitable production platform for supplying reagents to lead optimization, assays, and initial animal experiments in early development/drug discovery.

Read the article