THE RELEVANCE OF GLYCOSYLATION TO THE PRODUCTION OF RECOMBINANT GLYCOPROTEINS

Abstract

It is being increasingly recognised that many polypeptides of therapeutic interest, which in their native form are glycoproteins, need to be glycosylated in order to be of benefit in vivo..A consideration of polypeptide glycosylation therefore becomes relevant throughoutthe development and production of recombinant glycoproteins, principally for the following reasons. First, cell lines differ in their glycosylation characteristics, and the same polypeptide expressed in two different cell lines will generally be glycosylated differently. As a consequence, a recombinant glycoprotein is usually glycosylated differently to the native form, and such 'non-physiological' glycosylation can have profoundeffects on functional activity, physicochemical properties, and pharmacokinetic behaviour in vivo . A limited set of oligosaccharide determinants has been identified, the members of which influence the pharmacokinetic and immunogenic properties of a glycoprotein. It can therefore prove valuable to screen anycell line chosen for the production of a recombinant polypeptide, for expression of such determinants. Second, to ensurethat any changes in culture method (for example, during scale-up) are not associated with alterations in glycosylation, and that batch-to-batch uniformity is maintained during production,it is necessary to follow the glycosylation pattern of the secreted protein. Third, individual glycoformsof a polypeptide can differ with respect to functional properties. Identification of an improved product may, in some cases, involve nothing morethan isolation of a particular glycosylation variant. These and other aspects of the glycosylation of recombinant glycoproteins are discussed ir this paper.