DC Field | Value | Language |
---|---|---|
dc.contributor.author | Lee, Chung-Geun | - |
dc.contributor.author | Oh, Myung jin | - |
dc.contributor.author | PARK, SEUNG YEOL | - |
dc.contributor.author | An, Hyun Joo | - |
dc.contributor.author | Kim, Jung Hoe | - |
dc.date.accessioned | 2019-12-05T01:10:03Z | - |
dc.date.available | 2019-12-05T01:10:03Z | - |
dc.date.created | 2019-12-04 | - |
dc.date.issued | 2018-05 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.uri | https://oasis.postech.ac.kr/handle/2014.oak/100354 | - |
dc.description.abstract | Sialylation 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.language | English | - |
dc.publisher | Nature Publishing Group | - |
dc.relation.isPartOf | Scientific Reports | - |
dc.title | Inhibition of poly-LacNAc biosynthesis with release of CMP-Neu5Ac feedback inhibition increases the sialylation of recombinant EPO produced in CHO cells | - |
dc.type | Article | - |
dc.identifier.doi | 10.1038/s41598-018-25580-9 | - |
dc.type.rims | ART | - |
dc.identifier.bibliographicCitation | Scientific Reports, v.8 | - |
dc.identifier.wosid | 000431627300050 | - |
dc.citation.title | Scientific Reports | - |
dc.citation.volume | 8 | - |
dc.contributor.affiliatedAuthor | PARK, SEUNG YEOL | - |
dc.identifier.scopusid | 2-s2.0-85046833157 | - |
dc.description.journalClass | 1 | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | HAMSTER OVARY CELLS | - |
dc.subject.keywordPlus | HUMAN INTERFERON-GAMMA | - |
dc.subject.keywordPlus | HUMAN ERYTHROPOIETINS | - |
dc.subject.keywordPlus | ENHANCED SIALYLATION | - |
dc.subject.keywordPlus | MASS-SPECTROMETRY | - |
dc.subject.keywordPlus | GLYCOSYLATION | - |
dc.subject.keywordPlus | GLYCOPROTEINS | - |
dc.subject.keywordPlus | CULTURE | - |
dc.subject.keywordPlus | OLIGOSACCHARIDES | - |
dc.subject.keywordPlus | PROTEINS | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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