Enhanced sialylation and in vivo efficacy of recombinant human α-galactosidase through in vitro glycosylation

BMB Reports

Sung-Chul Jung^4¹  Heung-Rok Park^3²  Jung Mi Lee^2³  Youngsoo Sohn^1,3⁴ 

[1] Department of Biochemistry, School of Medicine, Ewha Womans University, Seoul 158-710, Korea^4;ISU ABXIS Co. Ltd, Seoul 120-752^3;Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-806^2;School of Chemical and Biological Engineering, Seoul National University, Seoul 151-742^1

关键词: Alpha-galactosidase A;   

DOI  :  

学科分类：生物化学/生物物理

来源: Korean Society for Biochemistry and Molecular Biology

【 摘 要 】

Human α-galactosidase A (GLA) has been used in enzyme replacement therapy for patients with Fabry disease. We expressed recombinant GLA from Chinese hamster ovary cells with very high productivity. When compared to an approved GLA (agalsidase beta), its size and charge were found to be smaller and more neutral. These differences resulted from the lack of terminal sialic acids playing essential roles in the serum half-life and proper tissue targeting. Because a simplesialylation reaction was not enough to increase the sialic acid content, a combined reaction using galactosyltransferase, sialyltransferase, and their sugar substrates at the same time was developed and optimized to reduce the incubation time. The product generated by this reaction had nearly the same size, isoelectric points, and sialic acid content as agalsidase beta. Furthermore, it had better in vivo efficacy to degrade the accumulated globotriaosylceramide in target organs of Fabry mice compared to an unmodified version.

【 授权许可】

Unknown