Abstract
Many of the most valuable recombinant DNA products, including monoclonal antibodies, are secreted glycoproteins, which contain N-glycans. The biochemical nature of these attached glycans depends on the characteristics of the host cell used, the protein synthesized, and the culture environment. The capacity to produce functional glycoproteins with desired glycosylation patterns depends on the presence of proper cellular enzymatic machinery required for the processing of N-glycans. It is well recongnized that expression of therapeutic proteins using insect cells in combination with the baculovirus-expression system has potential advantages in terms of the ease of large scale, low cost production of heterologous glycoproteins. However, the glycoforms expressed in several commonly used insect cell lines are markedly different from those expressed in human cells. As N-glycans often affect the in vivo biological activity, pharmacokinetics, and several other properties of glycoproteins, the glycoforms produced in this system have become a major concern in the last few years. Accordingly, considerable effort has been invested in the past decade in order to gain a better understanding of the processing of N-glycans in insect cells that generate different glycoforms, and also to overcome the bottlenecks to producing glycoproteins with humanized N-glycans that are more suitable for therapeutic use.
