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dc.contributor.authorLavado-García, Jesús
dc.contributor.authorJorge, Inmaculada 
dc.contributor.authorCervera, Laura
dc.contributor.authorVazquez, Jesus 
dc.contributor.authorGòdia, Francesc
dc.date.accessioned2020-05-08T07:37:53Z
dc.date.available2020-05-08T07:37:53Z
dc.date.issued2020-03-06
dc.identifier.citationJ Proteome Res. 2020; 19(3):1085-1099es_ES
dc.identifier.issn1535-3893es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/9971
dc.description.abstractThe production of virus-like particles (VLPs) has gained importance over the last few years owing to the benefits they provide compared to conventional vaccines. The biopharmaceutical industry is currently searching for safer candidates based on VLPs for new and existing vaccines and implementing new methods of manufacturing, thus allowing a more sustainable, effective, and species-specific production. Despite achieving lower yields compared to traditional platforms, the use of mammalian cells provides the right post-translational modifications, and consequently, the intensification of bioprocesses using mammalian cell platforms has become a matter of pressing concern. One of the methods subjected to intensification is transient gene expression, which has been proven to be highly effective regarding VLP production for preclinical or even clinical trials. In this work, a multiplexed quantitative proteomic approach has been applied to study the molecular characteristics of HEK293 cell cultures when growing at cell densities higher than 4 × 106 cells/mL and to study the effects related to cell transfection and VLP production. The obtained results revealed a set of functional and metabolic profiles of HEK293 under these three different conditions that allowed the identification of physiological bottlenecks regarding VLP production. Regarding the cell density effect, molecular alterations in the cell biology were proposed to help explain the difficulty for the cells to be transfected at higher densities. In addition, an overall disruption of cellular homeostasis after transfection was observed based on altered biological processes, and after identifying potential pathways liable to be optimized via metabolic engineering, different solutions were proposed to improve VLP production.es_ES
dc.description.sponsorshipThe project that gave rise to these results received the support of a fellowship from ”la Caixa” Foundation (ID 100010434). The fellowship code is LCF/BQ/ES17/11600003. This study was supported by competitive grants from the Spanish Ministry of Economy and Competitiveness (MINECO) (BIO2015-67580-P, PGC2018-097019-BI00) through the Carlos III Institute of Health-Fondo de Investigación Sanitaria (PRB3, PT17/0019/0003 ISCIIISGEFI/FEDER) and by CIBERCV (CB16/11/00277). The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).es_ES
dc.language.isoenges_ES
dc.publisherAmerican Chemical Society (ACS) es_ES
dc.type.hasVersionAMes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectHEK293es_ES
dc.subjectHIVes_ES
dc.subjectVLPes_ES
dc.subjectCell density effectes_ES
dc.subjectTransient transfectiones_ES
dc.titleMultiplexed Quantitative Proteomic Analysis of HEK293 Provides Insights into Molecular Changes Associated with the Cell Density Effect, Transient Transfection, and Virus-Like Particle Productiones_ES
dc.typejournal articlees_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.pubmedID31994890es_ES
dc.format.volume19es_ES
dc.format.number3es_ES
dc.format.page1085-1099es_ES
dc.identifier.doi10.1021/acs.jproteome.9b00601es_ES
dc.contributor.funderFundación La Caixa 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderFundación ProCNIC 
dc.description.peerreviewedes_ES
dc.embargo.terms2021-03-01es_ES
dc.identifier.e-issn1535-3907es_ES
dc.relation.publisherversionhttps://doi.org/10.1021/acs.jproteome.9b00601es_ES
dc.identifier.journalJournal of proteome researches_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Proteómica cardiovasculares_ES
dc.repisalud.institucionCNICes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SEV-2015-0505es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/BIO2015-67580-Pes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/PGC2018-097019-BI00es_ES
dc.rights.accessRightsopen accesses_ES


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Attribution-NonCommercial-NoDerivatives 4.0 Internacional