CHO cells are the predominant host for biotherapeutic protein expression, with roughly 70% of licensed biologics manufactured in CHO. Multiple attributes make CHO cells desirable for bioproduction including the ability to adapt to high-density suspension culture in serum-free and chemically-defined media and the incorporation of post-translational modifications that are biologically-active in humans. For these reasons, the ability to produce transient CHO-derived proteins early on during drug development is highly advantageous to minimize, as much as possible, changes in protein quality/function observed when moving from R&D to bioproduction. Unfortunately, CHO cells express lower levels of protein than HEK293 cells in existing transient systems, in some instances 50-100 times less than the best 293-based systems, and only modest titer improvements are obtained through the optimization of individual components of existing transient CHO workflows. To address the significant unmet need for higher transient CHO protein titers, systems-based approaches were employed whereby the latest advances in cell culture media, feeds, transfection reagents and expression enhancers were optimized in conjunction with a new high-expressing CHO cell clone to generate the ExpiCHO transient expression system, a system capable of generating gram per liter protein titers in 10-14 days. These advances allow for unprecedented access to CHO-derived proteins early on during candidate selection and may serve to revolutionize the use of CHO cells for transient protein expression during the drug development process.
Learning objectives:
- Understanding recent advances in mammalian transient protein expression and how they fit into existing workflows
- Differences and similarities between various cell types used for transient protein expression