Glycosylation profile of the recombinant acid alpha-glucosidase produced in the human cell line HKB-11

Abstract

The current treatment of Pompe disease, a lysosomal storage disorder, is performed by enzyme replacement therapy using human recombinant alpha-glycosidase, produced in Chinese hamster ovary (CHO) cells. Despite the satisfactory results, cases of serious immunological reactions have been reported due to the differences between the recombinant protein and the native one. There is a growing enthusiasm for the use of human cell lines as a platform for production of recombinant glycoproteins because of their ability to produce glycoproteins as close as possible to those naturally found in the human body, minimizing possible immunogenic reactions. Therefore, the aim of the present work is to analyze the glycosylation profile present in the glycoprotein produced by HKB-11 human cell line. For this both the intact protein and the N- and O-glycosylated structures as well as the monosaccharide content will be analyzed. This work is expected to evaluate the possibility of establishing an alternative platform for the production of this enzyme, capable of generating a product with lower immunogenicity. (AU)