Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/6685
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dc.contributor.authorGülce İz, Sultan-
dc.contributor.authorAnıl İnevi, Müge-
dc.contributor.authorSağlam Metiner, Pelin-
dc.contributor.authorAyyıldız Tamiş, Duygu-
dc.contributor.authorKisbet, Nazlı-
dc.date.accessioned2018-01-15T08:44:19Z-
dc.date.available2018-01-15T08:44:19Z-
dc.date.issued2018-01-
dc.identifier.citationGülce İz, S., Anıl İnevi, M., Sağlam Metiner, P., Ayyıldız Tamiş, D., and Kisbet, N. (2018). A BioDesign approach to obtain high yields of biosimilars by anti-apoptotic cell engineering: A case study to increase the production yield of anti-TNF alpha producing recombinant CHO cells. Applied Biochemistry and Biotechnology, 184(1), 303-322. doi:10.1007/s12010-017-2540-2en_US
dc.identifier.issn0273-2289-
dc.identifier.issn1559-0291-
dc.identifier.urihttp://doi.org/10.1007/s12010-017-2540-2-
dc.identifier.urihttp://hdl.handle.net/11147/6685-
dc.description.abstractRecent developments in medical biotechnology have facilitated to enhance the production of monoclonal antibodies (mAbs) and recombinant proteins in mammalian cells. Human mAbs for clinical applications have focused on three areas, particularly cancer, immunological disorders, and infectious diseases. Tumor necrosis factor alpha (TNF-α), which has both proinflammatory and immunoregulatory functions, is an important target in biopharmaceutical industry. In this study, a humanized anti-TNF-α mAb producing stable CHO cell line which produces a biosimilar of Humira (adalimumab) was used. Adalimumab is a fully human anti-TNF mAb among the top-selling mAb products in recent years as a biosimilar. Products from mammalian cell bioprocesses are a derivative of cell viability and metabolism, which is mainly disrupted by cell death in bioreactors. Thus, different strategies are used to increase the product yield. Suppression of apoptosis, also called anti-apoptotic cell engineering, is the most remarkable strategy to enhance lifetime of cells for a longer production period. In fact, using anti-apoptotic cell engineering as a BioDesign approach was inspired by nature; nature gives prolonged life span to some cells like stem cells, tumor cells, and memory B and T cells, and researchers have been using this strategy for different purposes. In this study, as a biomimicry approach, anti-apoptotic cell engineering was used to increase the anti-TNF-α mAb production from the humanized anti-TNF-α mAb producing stable CHO cell line by Bcl-xL anti-apoptotic protein. It was shown that transient transfection of CHO cells by the Bcl-xL anti-apoptotic protein expressing plasmid prolonged the cell survival rate and protected cells from apoptosis. The transient expression of Bcl-xL using CHO cells enhanced the anti-TNF-α production. The production of anti-TNF-α in CHO cells was increased up to 215 mg/L with an increase of 160% after cells were transfected with Bcl-xL expressing plasmid with polyethylenimine (PEI) reagent at the ratio of 1:6 (DNA:PEI). In conclusion, the anti-apoptotic efficacy of the Bcl-xL expressing plasmid in humanized anti-TNF-α MAb producing stable CHO cells is compatible with curative effect for high efficiency recombinant protein production. Thus, this model can be used for large-scale production of biosimilars through transient Bcl-xL gene expression as a cost-effective method.en_US
dc.description.sponsorshipTUBITAK project number 1919B011402737 (Sultan Gülce İz)en_US
dc.language.isoenen_US
dc.publisherHumana Pressen_US
dc.relation.ispartofApplied Biochemistry and Biotechnologyen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCell engineeringen_US
dc.subjectChinese hamster ovary cellsen_US
dc.subjectPolyethylenimine (PEI)en_US
dc.subjectTransient gene expression (TGE)en_US
dc.titleA BioDesign approach to obtain high yields of biosimilars by anti-apoptotic cell engineering: A case study to increase the production yield of anti-TNF alpha producing recombinant CHO cellsen_US
dc.typeArticleen_US
dc.authoridTR246425en_US
dc.institutionauthorAnıl İnevi, Müge-
dc.institutionauthorAnıl İnevi, Müge-
dc.departmentİzmir Institute of Technology. Bioengineeringen_US
dc.identifier.volume184en_US
dc.identifier.issue1en_US
dc.identifier.startpage303en_US
dc.identifier.endpage322en_US
dc.identifier.wosWOS:000419607700024en_US
dc.identifier.scopus2-s2.0-85021987269en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1007/s12010-017-2540-2-
dc.identifier.pmid28685239en_US
dc.relation.doi10.1007/s12010-017-2540-2en_US
dc.coverage.doi10.1007/s12010-017-2540-2en_US
dc.identifier.wosqualityQ3-
dc.identifier.scopusqualityQ2-
item.fulltextWith Fulltext-
item.openairetypeArticle-
item.cerifentitytypePublications-
item.grantfulltextopen-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
crisitem.author.dept03.01. Department of Bioengineering-
Appears in Collections:Bioengineering / Biyomühendislik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
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