Glycosylation control technologies for recombinant therapeutic proteins

Protein glycosylation is a very important quality attribute of any biopharmaceutical product as it affects the efficacy, serum half-life, and antigenicity of a molecule. The present expression hosts commercially utilized for a recombinant glycoprotein production generally cannot produce a desired and uniform glycan composition and generally exhibit non-human glycans that can lead to unwanted side effects. The authors provide a comprehensive review of various approaches which can be implemented to minimize the glycan heterogeneity for the production of the desired protein with improved glycoforms. The authors also describe that the industry standard expression systems such as mammalian, insect, and yeast are glycoengineered to produce human-like glycan composition of a recombinant product. This review summarizes the recent technologies used for the improvement of the glycan composition of the biotherapeutics, focusing largely on the selection of an appropriate expression host, glycoengineering, and upstream process optimization to control protein glycosylation and thus enhanced biological activity with fewer side effects. Here, we also suggest various approaches such as host and clone selection to achieve expected glycosylation in a recombinant protein. The cell culture, biochemical, and physical process parameters play a key role in the manufacturing of the desired glycoform of a therapeutic protein. Hence, these components are to be considered very carefully while developing such glycoproteins. Also, glycoengineering of production host to modulate the protein glycosylation is also recommended in the present review.