1. Enhanced sialylation and in vivo efficacy of recombinant human α-galactosidase through in vitro glycosylation
- Author
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Youngsoo Sohn, Jung Mi Lee, Heung-Rok Park, Sung-Chul Jung, Tai Hyun Park, and Doo-Byoung Oh
- Subjects
Alpha-galactosidase A ,Enzyme replacement therapy ,Fabry disease ,In vitro glycosylation ,Sialic acid ,Biology (General) ,QH301-705.5 ,Biochemistry ,QD415-436 - Abstract
Human α-galactosidase A (GLA) has been used in enzymereplacement therapy for patients with Fabry disease. Weexpressed recombinant GLA from Chinese hamster ovary cellswith very high productivity. When compared to an approvedGLA (agalsidase beta), its size and charge were found to besmaller and more neutral. These differences resulted from thelack of terminal sialic acids playing essential roles in the serumhalf-life and proper tissue targeting. Because a simplesialylation reaction was not enough to increase the sialic acidcontent, a combined reaction using galactosyltransferase,sialyltransferase, and their sugar substrates at the same timewas developed and optimized to reduce the incubation time.The product generated by this reaction had nearly the samesize, isoelectric points, and sialic acid content as agalsidasebeta. Furthermore, it had better in vivo efficacy to degrade theaccumulated globotriaosylceramide in target organs of Fabrymice compared to an unmodified version. [BMB Reports 2013;46(3): 157-162]
- Published
- 2013
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