Enhancing the sialylation of recombinant EPO produced in CHO cells via the inhibition of glycosphingolipid biosynthesis

Cited 5 time in webofscience Cited 0 time in scopus
  • Hit : 344
  • Download : 288
DC FieldValueLanguage
dc.contributor.authorKwak, Chan-Yeongko
dc.contributor.authorPark, Seung-Yeolko
dc.contributor.authorLee, Chung Geunko
dc.contributor.authorOkino, Nozomuko
dc.contributor.authorIto, Makotoko
dc.contributor.authorKim, Jung Hoeko
dc.date.accessioned2017-11-08T05:05:24Z-
dc.date.available2017-11-08T05:05:24Z-
dc.date.created2017-10-30-
dc.date.created2017-10-30-
dc.date.issued2017-10-
dc.identifier.citationSCIENTIFIC REPORTS, v.7-
dc.identifier.issn2045-2322-
dc.identifier.urihttp://hdl.handle.net/10203/226836-
dc.description.abstractSialylation regulates the in vivo half-life of recombinant therapeutic glycoproteins, affecting their therapeutic efficacy. Levels of the precursor molecule cytidine monophospho-N-acetylneuraminic acid (CMP-Neu5Ac) are considered a limiting factor in the sialylation of glycoproteins. Here, we show that by reducing the amount of intracellular CMP-Neu5Ac consumed for glycosphingolipid (GSL) biosynthesis, we can increase the sialylation of recombinant human erythropoietin (rhEPO) produced in CHO cells. Initially, we found that treating CHO cells with a potent inhibitor of GSL biosynthesis increases the sialylation of the rhEPO they produce. Then, we established a stable CHO cell line that produces rhEPO in the context of repression of the key GSL biosynthetic enzyme UDP-glucose ceramide glucosyltransferase (UGCG). These UGCG-depleted cells show reduced levels of gangliosides and significantly elevated levels of rhEPO sialylation. Upon further analysis of the resulting N-glycosylation pattern, we discovered that the enhanced rhEPO sialylation could be attributed to a decrease in neutral and mono-sialylated N-glycans and an increase in di-sialylated N-glycans. Our results suggest that the therapeutic efficacy of rhEPO produced in CHO cells can be improved by shunting intracellular CMP-Neu5Ac away from GSL biosynthesis and toward glycoprotein sialylation.-
dc.languageEnglish-
dc.publisherNATURE PUBLISHING GROUP-
dc.subjectHAMSTER OVARY CELLS-
dc.subjectGROWTH-FACTOR RECEPTOR-
dc.subjectSIALIC-ACID CONTENT-
dc.subjectGLUCOSYLCERAMIDE SYNTHASE-
dc.subjectINTERFERON-GAMMA-
dc.subjectINSECT CELLS-
dc.subjectGLYCOSYLATION-
dc.subjectERYTHROPOIETIN-
dc.subjectPROTEIN-
dc.subjectEXPRESSION-
dc.titleEnhancing the sialylation of recombinant EPO produced in CHO cells via the inhibition of glycosphingolipid biosynthesis-
dc.typeArticle-
dc.identifier.wosid000412950600050-
dc.identifier.scopusid2-s2.0-85031300343-
dc.type.rimsART-
dc.citation.volume7-
dc.citation.publicationnameSCIENTIFIC REPORTS-
dc.identifier.doi10.1038/s41598-017-13609-4-
dc.contributor.localauthorKim, Jung Hoe-
dc.contributor.nonIdAuthorPark, Seung-Yeol-
dc.contributor.nonIdAuthorOkino, Nozomu-
dc.contributor.nonIdAuthorIto, Makoto-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
dc.subject.keywordPlusHAMSTER OVARY CELLS-
dc.subject.keywordPlusGROWTH-FACTOR RECEPTOR-
dc.subject.keywordPlusSIALIC-ACID CONTENT-
dc.subject.keywordPlusGLUCOSYLCERAMIDE SYNTHASE-
dc.subject.keywordPlusINTERFERON-GAMMA-
dc.subject.keywordPlusINSECT CELLS-
dc.subject.keywordPlusGLYCOSYLATION-
dc.subject.keywordPlusERYTHROPOIETIN-
dc.subject.keywordPlusPROTEIN-
dc.subject.keywordPlusEXPRESSION-
This item is cited by other documents in WoS
⊙ Detail Information in WoSⓡ Click to see webofscience_button
⊙ Cited 5 items in WoS Click to see citing articles in records_button

qr_code

  • mendeley

    citeulike


rss_1.0 rss_2.0 atom_1.0