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

Cited 8 time in scopus
Metadata Downloads
Title
Enhanced sialylation and in vivo efficacy of recombinant human α-galactosidase through in vitro glycosylation
Author(s)
Y Sohn; J M Lee; H R Park; S C Jung; T H Park; Doo-Byoung Oh
Bibliographic Citation
BMB Reports, vol. 46, no. 3, pp. 157-162
Publication Year
2013
Abstract
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 simple sialylation 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.
Keyword
Alpha-galactosidase AEnzyme replacement therapyFabry diseaseIn vitro glycosylationSialic acid
ISSN
1225-8687
Publisher
Korea Soc-Assoc-Inst
DOI
http://dx.doi.org/10.5483/BMBRep.2013.46.3.192
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
Files in This Item:
  • There are no files associated with this item.


Items in OpenAccess@KRIBB are protected by copyright, with all rights reserved, unless otherwise indicated.