Inhibition of poly-LacNAc biosynthesis with release of CMP-Neu5Ac feedback inhibition increases the sialylation of recombinant EPO produced in CHO cells

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dc.contributor.authorLee, Chung Geunko
dc.contributor.authorOh, Myung Jinko
dc.contributor.authorPark, Seung-Yeolko
dc.contributor.authorAn, Hyun Jooko
dc.contributor.authorKim, Jung Hoeko
dc.date.accessioned2018-05-24T02:42:39Z-
dc.date.available2018-05-24T02:42:39Z-
dc.date.created2018-05-21-
dc.date.created2018-05-21-
dc.date.created2018-05-21-
dc.date.issued2018-05-
dc.identifier.citationSCIENTIFIC REPORTS, v.8-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/10203/242339-
dc.description.abstractSialylation of recombinant therapeutic glycoproteins modulates their pharmacokinetic properties by affecting their in vivo half-life. N-glycan branching on glycoproteins increases the number of potential attachment sites for sialic acid. Here, we introduce a new approach for increasing the sialylation of recombinant human erythropoietin (rhEPO) produced in CHO cells by modulating poly-N-acetyllactosamine (poly-LacNAc) biosynthesis. We did not observe an increase in rhEPO sialylation, however, until the feedback inhibition by intracellular cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), which is a limiting factor for sialylation, was released. Thus, we found that a combined approach inhibiting poly-LacNAc biosynthesis and releasing CMP-Neu5Ac feedback inhibition produces the most significant increase in rhEPO sialylation in metabolically engineered CHO cells. Furthermore, a detailed analysis of the resulting N-glycan structures using LC/MS revealed increased tri- and tetra-sialylated N-glycan structures accompanied by a reduction of di-sialylated N-glycan structures. These results validate our new approach for glycosylation engineering, and we expect this approach will be useful in future efforts to enhance the efficacy of other therapeutic glycoproteins.-
dc.languageEnglish-
dc.publisherNATURE PUBLISHING GROUP-
dc.subjectHAMSTER OVARY CELLS-
dc.subjectHUMAN INTERFERON-GAMMA-
dc.subjectHUMAN ERYTHROPOIETINS-
dc.subjectENHANCED SIALYLATION-
dc.subjectMASS-SPECTROMETRY-
dc.subjectGLYCOSYLATION-
dc.subjectGLYCOPROTEINS-
dc.subjectCULTURE-
dc.subjectOLIGOSACCHARIDES-
dc.subjectPROTEINS-
dc.titleInhibition of poly-LacNAc biosynthesis with release of CMP-Neu5Ac feedback inhibition increases the sialylation of recombinant EPO produced in CHO cells-
dc.typeArticle-
dc.identifier.wosid000431627300050-
dc.identifier.scopusid2-s2.0-85046833157-
dc.type.rimsART-
dc.citation.volume8-
dc.citation.publicationnameSCIENTIFIC REPORTS-
dc.identifier.doi10.1038/s41598-018-25580-9-
dc.contributor.localauthorKim, Jung Hoe-
dc.contributor.nonIdAuthorOh, Myung Jin-
dc.contributor.nonIdAuthorPark, Seung-Yeol-
dc.contributor.nonIdAuthorAn, Hyun Joo-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusHAMSTER OVARY CELLS-
dc.subject.keywordPlusHUMAN INTERFERON-GAMMA-
dc.subject.keywordPlusHUMAN ERYTHROPOIETINS-
dc.subject.keywordPlusENHANCED SIALYLATION-
dc.subject.keywordPlusMASS-SPECTROMETRY-
dc.subject.keywordPlusGLYCOSYLATION-
dc.subject.keywordPlusGLYCOPROTEINS-
dc.subject.keywordPlusCULTURE-
dc.subject.keywordPlusOLIGOSACCHARIDES-
dc.subject.keywordPlusPROTEINS-
dc.subject.keywordPlusHAMSTER OVARY CELLS-
dc.subject.keywordPlusHUMAN INTERFERON-GAMMA-
dc.subject.keywordPlusHUMAN ERYTHROPOIETINS-
dc.subject.keywordPlusENHANCED SIALYLATION-
dc.subject.keywordPlusMASS-SPECTROMETRY-
dc.subject.keywordPlusGLYCOSYLATION-
dc.subject.keywordPlusGLYCOPROTEINS-
dc.subject.keywordPlusCULTURE-
dc.subject.keywordPlusOLIGOSACCHARIDES-
dc.subject.keywordPlusPROTEINS-
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