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dc.creatorGugliotta, Agustina-
dc.creatorCeaglio, Natalia Analia-
dc.creatorRaud, Brenda-
dc.creatorForno, Angela Guillermina-
dc.creatorMauro, Laura Valeria-
dc.creatorKratje, Ricardo Bertoldo-
dc.creatorOggero Eberhardt, Marcos Rafael-
dc.date2019-02-27T20:37:59Z-
dc.date2019-02-27T20:37:59Z-
dc.date2017-03-
dc.date2019-02-27T12:51:21Z-
dc.date.accessioned2019-04-29T15:43:05Z-
dc.date.available2019-04-29T15:43:05Z-
dc.date.issued2017-03-
dc.identifierGugliotta, Agustina; Ceaglio, Natalia Analia; Raud, Brenda; Forno, Angela Guillermina; Mauro, Laura Valeria; et al.; Glycosylation and antiproliferative activity of hyperglycosylated IFN-α2 potentiate HEK293 cells as biofactories; Elsevier Science; European Journal Of Pharmaceutics And Biopharmaceutics; 112; 3-2017; 119-131-
dc.identifier0939-6411-
dc.identifierhttp://hdl.handle.net/11336/70926-
dc.identifierCONICET Digital-
dc.identifierCONICET-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/300247-
dc.descriptionBoth CHO and HEK cells are interesting hosts for the production of biotherapeutics due to their ability to introduce post-translational modifications such as glycosylation. Even though oligosaccharide structures attached to proteins are conserved among eukaryotes, many differences have been found between therapeutic glycoproteins expressed in hamster and human derived cells. In this work, a hyperglycosylated IFN-α2b mutein (IFN4N) was produced in CHO and HEK cell lines and an extensive characterization of their properties was performed. IFN4NCHO exhibited a higher average molecular mass and more acidic isoforms compared to IFN4NHEK. In agreement with these results, a 2-times higher sialic acid content was found for IFN4NCHO in comparison with the HEK-derived protein. This result was in agreement with monosaccharide quantification and glycan's analysis using WAX chromatography and HILIC coupled to mass spectrometry; all methods supported the existence of highly sialylated and also branched structures for IFN4NCHO glycans, in contrast with smaller and truncated structures among IFN4NHEK glycans. Unexpectedly, those remarkable differences in the glycosylation pattern had not a considerable impact on the clearance rate of both molecules in rats. In fact, although IFN4NHEK reached maximum plasma concentration 3-times faster than IFN4NCHO, their elimination profile did not differ significantly. Also, despite the in vitro antiviral specific biological activity of both proteins was the same, IFN4NHEK was more efficient as an antiproliferative agent in different tumor-derived cell lines. Accordingly, IFN4NHEK showed a higher in vivo antitumor activity in animal models. Our results show the importance of an appropriate host selection to set up a bioprocess and potentiate the use of HEK293 cells for the production of a new hyperglycosylated protein-based pharmaceutical.-
dc.descriptionFil: Gugliotta, Agustina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina-
dc.descriptionFil: Ceaglio, Natalia Analia. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina-
dc.descriptionFil: Raud, Brenda. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina-
dc.descriptionFil: Forno, Angela Guillermina. Universidad Nacional del Litoral; Argentina. Zelltek; Argentina-
dc.descriptionFil: Mauro, Laura Valeria. Zelltek; Argentina-
dc.descriptionFil: Kratje, Ricardo Bertoldo. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina-
dc.descriptionFil: Oggero Eberhardt, Marcos Rafael. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Laboratorio de Cultivos Celulares; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina-
dc.formatapplication/pdf-
dc.formatapplication/pdf-
dc.formatapplication/pdf-
dc.formatapplication/pdf-
dc.languageeng-
dc.publisherElsevier Science-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/https://doi.org/10.1016/j.ejpb.2016.11.012-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0939641116308098-
dc.rightsinfo:eu-repo/semantics/restrictedAccess-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/-
dc.sourcereponame:CONICET Digital (CONICET)-
dc.sourceinstname:Consejo Nacional de Investigaciones Científicas y Técnicas-
dc.sourceinstacron:CONICET-
dc.subjectANTITUMORAL ACTIVITY-
dc.subjectCHO CELLS-
dc.subjectGLYCOPROTEINS-
dc.subjectHEK293 CELLS-
dc.subjectHYPERGLYCOSYLATED IFN-Α2B-
dc.subjectN-GLYCOSYLATION-
dc.subjectPHARMACOKINETICS-
dc.subjectOtras Biotecnologías de la Salud-
dc.subjectBiotecnología de la Salud-
dc.subjectCIENCIAS MÉDICAS Y DE LA SALUD-
dc.titleGlycosylation and antiproliferative activity of hyperglycosylated IFN-α2 potentiate HEK293 cells as biofactories-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
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