The biopharmaceutical market is growing at a significant pace, with two production systems dominating – mammalian cell culture and microbial fermentation.
With the exception of large macromolecules such as full-length monoclonal antibodies and bi-specifics, most therapeutic protein classes are made in microbial systems, including recombinant proteins, enzymes, subunit vaccines, as well as novel formats such as antibody mimetics, antibody fragments, and nanobodies. This is especially the case where protein glycosylation is not a functional requirement.
Bacteria, the microbial workhorse expression system, is actually three systems in one. The bacterial cell has the choice of production in the cytoplasm, the periplasm, or inclusion bodies (IBs). This diversity in production channels reflects the diversity of proteins expressed and often the cell decides which route is best. For example, the periplasm is typically preferred to fold proteins that are more complex and containing disulfide bonds; however, producing insoluble protein in IB's can and often is more economical from a bioprocessing perspective.
IBs have historically suffered a bad reputation. During this webinar, we discuss them in a different light; we explain the pros and cons of soluble and insoluble processes, share our experience with isolating, solubilizing and properly re-folding, and argue that the right approach to insoluble processes can not only be viable at scale but can offer great opportunities for yield improvement versus soluble production. We also discuss our strategies and future innovation to improve the performance of our IB processes.
Key learning objectives:
- Differences between soluble and insoluble processes
- Approaches for isolating, solubilizing and properly re-folding proteins from inclusion bodies
- Strategies used for successful scale up of an IB process