Plethora of Potential Platforms: a review of current and future trends in expression system choice in the biopharmaceutical industry /

Abstract

In the thirty years since the first biopharmaceuticals were approved for use in humans, the choice of expression system for new biopharmaceuticals has remained largely unchanged and is still mainly determined by the necessity of human-like post translation modifications, such as glycosylation, for the required method of action of the therapeutic protein. Currently, those biopharmaceuticals requiring post translational modifications are overwhelming expressed in mammalian systems, while those that do not are expressed in microbial systems. Chinese Hamster Ovary and Escherichia coli are the overwhelming front-runners, respectively, with over 85% of all biopharmaceuticals between them. While alternative systems such as methylotrophic yeast, human, transgenic animals, insects and plants have all made the leap to commercial manufacture, the inherent conservatism of the industry and regulatory authorities, and the inefficient or non-human glycosylation patterns have so far precluded alternative expression systems from displacing the dominant platforms outside a few niche areas. Expanding knowledge of glycosylation pathways and new genetic engineering tools, especially the site-specific CRISPR/Cas9 nucleases, offer a path forward for a wider choice of expression platforms to meet the ever-expanding needs of the biopharmaceutical industry.