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KMID : 0624620130460030157
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BMB Reports
2013 Volume.46 No. 3 p.157 ~ p.162
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Enhanced sialylation and in vivo efficacy of recombinant human α-galactosidase through in vitro glycosylation
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Sohn Young-Soo
Lee Jung-Mi
Park Heung-Rok
Jung Sung-Chul
Park Tai-Hyun
Oh Doo-Byoung
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Abstract
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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.
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KEYWORD
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Alpha-galactosidase A, Enzyme replacement therapy, Fabry disease, In vitro glycosylation, Sialic acid
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