{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T03:49:14Z","timestamp":1776829754165,"version":"3.51.2"},"reference-count":69,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T00:00:00Z","timestamp":1698192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia\/Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (FCT\/MCTES, Portugal) through national funds to iNOVA4Health","doi-asserted-by":"publisher","award":["UIDB\/04462\/2020"],"award-info":[{"award-number":["UIDB\/04462\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia\/Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (FCT\/MCTES, Portugal) through national funds to iNOVA4Health","doi-asserted-by":"publisher","award":["UIDP\/04462\/2020"],"award-info":[{"award-number":["UIDP\/04462\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia\/Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (FCT\/MCTES, Portugal) through national funds to iNOVA4Health","doi-asserted-by":"publisher","award":["LA\/P\/0087\/2020"],"award-info":[{"award-number":["LA\/P\/0087\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia\/Minist\u00e9rio da Ci\u00eancia, Tecnologia e Ensino Superior (FCT\/MCTES, Portugal) through national funds to iNOVA4Health","doi-asserted-by":"publisher","award":["2020.01216.CEECIND"],"award-info":[{"award-number":["2020.01216.CEECIND"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Associate Laboratory LS4FUTURE","doi-asserted-by":"publisher","award":["UIDB\/04462\/2020"],"award-info":[{"award-number":["UIDB\/04462\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Associate Laboratory LS4FUTURE","doi-asserted-by":"publisher","award":["UIDP\/04462\/2020"],"award-info":[{"award-number":["UIDP\/04462\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Associate Laboratory LS4FUTURE","doi-asserted-by":"publisher","award":["LA\/P\/0087\/2020"],"award-info":[{"award-number":["LA\/P\/0087\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Associate Laboratory LS4FUTURE","doi-asserted-by":"publisher","award":["2020.01216.CEECIND"],"award-info":[{"award-number":["2020.01216.CEECIND"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Stimulus of Scientific Employment, Individual Support program","award":["UIDB\/04462\/2020"],"award-info":[{"award-number":["UIDB\/04462\/2020"]}]},{"name":"Stimulus of Scientific Employment, Individual Support program","award":["UIDP\/04462\/2020"],"award-info":[{"award-number":["UIDP\/04462\/2020"]}]},{"name":"Stimulus of Scientific Employment, Individual Support program","award":["LA\/P\/0087\/2020"],"award-info":[{"award-number":["LA\/P\/0087\/2020"]}]},{"name":"Stimulus of Scientific Employment, Individual Support program","award":["2020.01216.CEECIND"],"award-info":[{"award-number":["2020.01216.CEECIND"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>Monoclonal antibody-based therapy has shown efficacy against cancer, autoimmune, infectious, and inflammatory diseases. Multispecific antibodies (MsAbs), including trispecifics (tsAbs), offer enhanced therapeutic potential by targeting different epitopes. However, when co-expressed from three or more different polypeptide chains, MsAb production can lead to incorrect chain assembly and co-production of mispaired species with impaired biological activity. Moreover, mispairing carries significant challenges for downstream purification, decreasing yields and increasing the cost of bioprocess development. In this study, quantitative transcriptomics and proteomics analyses were employed to investigate which signaling pathways correlated with low and high mispairing clone signatures. Gene and protein expression profiles of Chinese hamster ovary (CHO) clones producing an tsAb were analyzed in the exponential growth and stationary (tsAb production) phase of fed-batch culture. Functional analysis revealed activated endoplasmic reticulum stress in high mispairing clones in both culture phases, while low mispairing clones exhibited expression profiles indicative of activated protein translation, as well as higher endocytosis and target protein degradation, suggesting the clearance of unfolded proteins through ubiquitin-mediated mechanisms. In addition, through transcriptomic profiling, we identified a group of genes that have the potential to be used as a biomarker panel tool for identifying high mispairing levels in the early stages of bioprocess development.<\/jats:p>","DOI":"10.3390\/biomedicines11112890","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T09:54:08Z","timestamp":1698227648000},"page":"2890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Identification of Mispairing Omic Signatures in Chinese Hamster Ovary (CHO) Cells Producing a Tri-Specific Antibody"],"prefix":"10.3390","volume":"11","author":[{"given":"Maria Jo\u00e3o","family":"Sebasti\u00e3o","sequence":"first","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2780-901 Oeiras, Portugal"},{"name":"ITQB-NOVA, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"given":"Michael","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Sanofi Cell Line and Cell Bank Development, Mammalian Platform, Global CMC Development, Framingham, MA 01701, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4857-9413","authenticated-orcid":false,"given":"Jos\u00e9","family":"Escandell","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2780-901 Oeiras, Portugal"},{"name":"ITQB-NOVA, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]},{"given":"Fatemeh","family":"Tousi","sequence":"additional","affiliation":[{"name":"Sanofi Bioanalytics Development, Global CMC Development, Framingham, MA 01701, USA"}]},{"given":"Jin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Sanofi Cell Line and Cell Bank Development, Mammalian Platform, Global CMC Development, Framingham, MA 01701, USA"}]},{"given":"Bruno","family":"Figueroa","sequence":"additional","affiliation":[{"name":"Sanofi Cell Line and Cell Bank Development, Mammalian Platform, Global CMC Development, Framingham, MA 01701, USA"}]},{"given":"Christine","family":"DeMaria","sequence":"additional","affiliation":[{"name":"Sanofi Cell Line and Cell Bank Development, Mammalian Platform, Global CMC Development, Framingham, MA 01701, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7245-6785","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Gomes-Alves","sequence":"additional","affiliation":[{"name":"iBET, Instituto de Biologia Experimental e Tecnol\u00f3gica, Apartado 12, 2780-901 Oeiras, Portugal"},{"name":"ITQB-NOVA, Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier, Universidade Nova de Lisboa, Av. da Rep\u00fablica, 2780-157 Oeiras, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/256495a0","article-title":"Continuous cultures of fused cells secreting antibody of predefined specificity","volume":"256","author":"Milstein","year":"1975","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5909","DOI":"10.1074\/jbc.RA118.001752","article-title":"A biparatopic agonistic antibody that mimics fibroblast growth factor 21 ligand activity","volume":"293","author":"Shi","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1038\/nm.2942","article-title":"A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model","volume":"18","author":"Kitazawa","year":"2012","journal-title":"Nat. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1177\/2040620718799997","article-title":"The role of emicizumab, a bispecific factor IXa- and factor X-directed antibody, for the prevention of bleeding episodes in patients with hemophilia A","volume":"9","author":"Knight","year":"2018","journal-title":"Ther. Adv. Hematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1038\/s41375-018-0014-3","article-title":"Simultaneous multiple interaction T-cell engaging (SMITE) bispecific antibodies overcome bispecific T-cell engager (BiTE) resistance via CD28 co-stimulation","volume":"32","author":"Correnti","year":"2018","journal-title":"Leukemia"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.3109\/10428194.2016.1161185","article-title":"Blinatumomab: A CD19\/CD3 bispecific T cell engager (BiTE) with unique anti-tumor efficacy","volume":"57","author":"Goebeler","year":"2016","journal-title":"Leuk. Lymphoma"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.pharmthera.2017.12.002","article-title":"Bispecific antibodies for cancer therapy: A review","volume":"185","author":"Krishnamurthy","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1038\/s43018-019-0004-z","article-title":"Trispecific antibodies enhance the therapeutic efficacy of tumor-directed T cells through T cell receptor co-stimulation","volume":"1","author":"Wu","year":"2019","journal-title":"Nat. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/s41586-022-04439-0","article-title":"A trispecific antibody targeting HER2 and T cells inhibits breast cancer growth via CD4 cells","volume":"603","author":"Seung","year":"2022","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1126\/science.aan8630","article-title":"Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques","volume":"358","author":"Xu","year":"2017","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"129","DOI":"10.4161\/mabs.2.2.11221","article-title":"Catumaxomab: Clinical Development and Future Directions","volume":"2","author":"Linke","year":"2010","journal-title":"mAbs"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1158\/1078-0432.CCR-18-2337","article-title":"FDA Approval: Blinatumomab for Patients with B-cell Precursor Acute Lymphoblastic Leukemia in Morphologic Remission with Minimal Residual Disease","volume":"25","author":"Jen","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.cllc.2022.11.004","article-title":"Amivantamab, an Epidermal Growth Factor Receptor (EGFR) and Mesenchymal-epithelial Transition Factor (MET) Bispecific Antibody, Designed to Enable Multiple Mechanisms of Action and Broad Clinical Applications","volume":"24","author":"Cho","year":"2022","journal-title":"Clin. Lung Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.ophtha.2019.03.023","article-title":"Simultaneous Inhibition of Angiopoietin-2 and Vascular Endothelial Growth Factor-A with Faricimab in Diabetic Macular Edema BOULEVARD Phase 2 Randomized Trial","volume":"126","author":"Sahni","year":"2019","journal-title":"Ophthalmology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.tibtech.2013.08.007","article-title":"A tale of two specificities: Bispecific antibodies for therapeutic and diagnostic applications","volume":"31","author":"Byrne","year":"2013","journal-title":"Trends Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jviromet.2008.05.023","article-title":"A rapid point of care immunoswab assay for SARS-CoV detection","volume":"152","author":"Kammila","year":"2008","journal-title":"J. Virol. Methods"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5876","DOI":"10.1021\/ac203403d","article-title":"Bispecific Antibody-Mediated Detection of the Staphylococcus aureus Thermonuclease","volume":"84","author":"Wagstaffe","year":"2012","journal-title":"Anal. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"26","DOI":"10.17145\/jab.20.005","article-title":"Engineered Technologies and Bioanalysis of multispecific Antibody Formats","volume":"6","author":"Amaral","year":"2020","journal-title":"J. Appl. Bioanal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1021\/acs.analchem.9b05018","article-title":"Intact Protein Mass Spectrometry of Cell Culture Harvest Guides Cell Line Development for Trispecific Antibodies","volume":"92","author":"Tousi","year":"2020","journal-title":"Anal. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41423-020-0417-8","article-title":"Challenges and strategies for next-generation bispecific antibody-based antitumor therapeutics","volume":"17","author":"Li","year":"2020","journal-title":"Cells Mol. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1093\/protein\/9.7.617","article-title":"\u2018Knobs-into-holes\u2019 engineering of antibody CH3 domains for heavy chain heterodimerization","volume":"9","author":"Ridgway","year":"1996","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1093\/protein\/gzq034","article-title":"VH\/VL interface engineering to promote selective expression and inhibit conformational isomerization of thrombopoietin receptor agonist single-chain diabody","volume":"23","author":"Igawa","year":"2010","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1955433","DOI":"10.1080\/19420862.2021.1955433","article-title":"An end-to-end automated platform process for high-throughput engineering of next-generation multi-specific antibody therapeutics","volume":"13","author":"Furtmann","year":"2021","journal-title":"mAbs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.pep.2018.11.011","article-title":"A brief introduction of IgG-like bispecific antibody purification: Methods for removing product-related impurities","volume":"155","author":"Li","year":"2019","journal-title":"Protein Expr. Purif."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1080\/19420862.2018.1511198","article-title":"A systematic approach for analysis and characterization of mispairing in bispecific antibodies with asymmetric architecture","volume":"10","author":"Wang","year":"2018","journal-title":"mAbs"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jbiotec.2017.01.004","article-title":"Expansion of 3D human induced pluripotent stem cell aggregates in bioreactors: Bioprocess intensification and scaling-up approaches","volume":"246","author":"Abecasis","year":"2017","journal-title":"J. Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.trsl.2019.09.001","article-title":"Bioreactor-based 3D human myocardial ischemia\/reperfusion in vitro model: A novel tool to unveil key paracrine factors upon acute myocardial infarction","volume":"215","author":"Reis","year":"2020","journal-title":"Transl. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nmeth.3901","article-title":"The Perseus computational platform for comprehensive analysis of (prote)omics data","volume":"13","author":"Tyanova","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4003","DOI":"10.1091\/mbc.e04-04-0293","article-title":"The Cochaperone HspBP1 Inhibits the CHIP Ubiquitin Ligase and Stimulates the Maturation of the Cystic Fibrosis Transmembrane Conductance Regulator","volume":"15","author":"Alberti","year":"2004","journal-title":"Mol. Biol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1002\/bit.27347","article-title":"Tailoring translational strength using Kozak sequence variants improves bispecific antibody assembly and reduces product-related impurities in CHO cells","volume":"117","author":"Blanco","year":"2020","journal-title":"Biotechnol. Bioeng."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zhong, X., and D\u2019antona, A.M. (2021). Recent Advances in the Molecular Design and Applications of Multispecific Biotherapeutics. Antibodies, 10.","DOI":"10.3390\/antib10020013"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1002\/bit.26803","article-title":"Culture temperature modulates half antibody and aggregate formation in a Chinese hamster ovary cell line expressing a bispecific antibody","volume":"115","author":"Gomez","year":"2018","journal-title":"Biotechnol. Bioeng."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"16620","DOI":"10.1038\/s41598-020-73573-4","article-title":"Perfusion reduces bispecific antibody aggregation via mitigating mitochondrial dysfunction-induced glutathione oxidation and ER stress in CHO cells","volume":"10","author":"Sinharoy","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4305","DOI":"10.1002\/bit.27899","article-title":"Multi-omics profiling of a CHO cell culture system unravels the effect of culture pH on cell growth, antibody titer, and product quality","volume":"118","author":"Lee","year":"2021","journal-title":"Biotechnol. Bioeng."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ymben.2019.11.007","article-title":"Engineering of Chinese hamster ovary cell lipid metabolism results in an expanded ER and enhanced recombinant biotherapeutic protein production","volume":"57","author":"Budge","year":"2020","journal-title":"Metab. Eng."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/bit.25116","article-title":"Model-directed engineering of \u201cdifficult-to-express\u201d monoclonal antibody production by Chinese hamster ovary cells","volume":"111","author":"Pybus","year":"2014","journal-title":"Biotechnol. Bioeng."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.jbiotec.2009.02.014","article-title":"Heterologous expression of the lipid transfer protein CERT increases therapeutic protein productivity of mammalian cells","volume":"141","author":"Florin","year":"2009","journal-title":"J. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1002\/bit.25687","article-title":"Integrated cell and process engineering for improved transient production of a \u201cdifficult-to-express\u201d fusion protein by CHO cells","volume":"112","author":"Johari","year":"2015","journal-title":"Biotechnol. Bioeng."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1021\/pr501027c","article-title":"High-Antibody-Producing Chinese Hamster Ovary Cells Up-Regulate Intracellular Protein Transport and Glutathione Synthesis","volume":"14","author":"Orellana","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1038\/nbt.3280","article-title":"Engineered CHO cells for production of diverse, homogeneous glycoproteins","volume":"33","author":"Yang","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1002\/biot.201400663","article-title":"Dynamics of immature mAb glycoform secretion during CHO cell culture: An integrated modelling framework","volume":"11","author":"Fan","year":"2016","journal-title":"Biotechnol. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jbiotec.2018.05.018","article-title":"Clonal variation in productivity and proteolytic clipping of an Fc-fusion protein in CHO cells: Proteomic analysis suggests a role for defective protein folding and the UPR","volume":"281","author":"Henry","year":"2018","journal-title":"J. Biotechnol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3744","DOI":"10.1002\/bit.27850","article-title":"Expression liabilities in a four-chain bispecific molecule","volume":"118","author":"Guo","year":"2021","journal-title":"Biotechnol. Bioeng."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/btpr.1767","article-title":"Free light chain content in culture media reflects recombinant monoclonal antibody productivity and quality","volume":"29","author":"Bhoskar","year":"2013","journal-title":"Biotechnol. Prog."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Magistrelli, G., Pontini, G., Poitevin, Y., Malinge, P., Bourguignon, J., Gauye, F., Fleury, E., Pl\u00e8che, N., Galissaires, L., and Fischer, N. (2018). Tuning Relative Polypeptide Expression to Optimize Assembly, Yield and Downstream Processing of Bispecific Antibodies. Antibodies, 7.","DOI":"10.3390\/antib7030029"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.jbiotec.2013.03.019","article-title":"Control of IgG LC:HC ratio in stably transfected CHO cells and study of the impact on expression, aggregation, glycosylation and conformational stability","volume":"165","author":"Ho","year":"2013","journal-title":"J. Biotechnol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.febslet.2006.11.062","article-title":"hnRNP-U enhances the expression of specific genes by stabilizing mRNA","volume":"581","author":"Yugami","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/wrna.1327","article-title":"Diverse roles of the nucleic acid-binding protein KHSRP in cell differentiation and disease","volume":"7","author":"Briata","year":"2015","journal-title":"Wiley Interdiscip. Rev. RNA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0079-6603(02)71046-5","article-title":"A History of Poly A Sequences: From Formation to Factors to Function","volume":"71","author":"Edmonds","year":"2002","journal-title":"Prog. Nucleic Acid Res. Mol. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1042\/BJ20141453","article-title":"ABC50 mutants modify translation start codon selection","volume":"467","author":"Stewart","year":"2015","journal-title":"Biochem. J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5750","DOI":"10.1074\/jbc.M401988200","article-title":"Fragile X-related Protein FXR1P Regulates Proinflammatory Cytokine Tumor Necrosis Factor Expression at the Post-transcriptional Level","volume":"280","author":"Garnon","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/s41556-018-0045-z","article-title":"Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation","volume":"20","author":"Huang","year":"2018","journal-title":"Nat. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"125","DOI":"10.5483\/BMBRep.2022.55.3.188","article-title":"The translational landscape as regulated by the RNA helicase DDX3","volume":"55","author":"Park","year":"2022","journal-title":"BMB Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/sj.onc.1210687","article-title":"Candidate tumor suppressor DDX3 RNA helicase specifically represses cap-dependent translation by acting as an eIF4E inhibitory protein","volume":"27","author":"Shih","year":"2007","journal-title":"Oncogene"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5336","DOI":"10.1093\/nar\/gkab287","article-title":"DDX3 depletion represses translation of mRNAs with complex 5\u2032 UTRs","volume":"49","author":"Calviello","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41580-020-0250-z","article-title":"Mechanisms, regulation and functions of the unfolded protein response","volume":"21","author":"Hetz","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Samy, A., Kaneyoshi, K., and Omasa, T. (2020). Improvement of Intracellular Traffic System by Overexpression of KDEL Receptor 1 in Antibody-Producing CHO Cells. Biotechnol. J., 15.","DOI":"10.1002\/biot.201900352"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1111\/jcmm.16255","article-title":"Regulation of lipid metabolism by the unfolded protein response","volume":"25","author":"Moncan","year":"2021","journal-title":"J. Cells Mol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1194\/jlr.M064022","article-title":"SREBP-2-deficient and hypomorphic mice reveal roles for SREBP-2 in embryonic development and SREBP-1c expression","volume":"57","author":"Vergnes","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1194\/jlr.M300203-JLR200","article-title":"Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice","volume":"44","author":"Maxwell","year":"2003","journal-title":"J. Lipid Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"12027","DOI":"10.1073\/pnas.1534923100","article-title":"Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes","volume":"100","author":"Horton","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1247\/csf.16005","article-title":"MLX Is a Transcriptional Repressor of the Mammalian Golgi Stress Response","volume":"41","author":"Taniguchi","year":"2016","journal-title":"Cell Struct. Funct."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/ni1147","article-title":"Access of soluble antigens to the endoplasmic reticulum can explain cross-presentation by dendritic cells","volume":"6","author":"Ackerman","year":"2005","journal-title":"Nat. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/j.cell.2008.12.009","article-title":"Tracing the Retrograde Route in Protein Trafficking","volume":"135","author":"Johannes","year":"2008","journal-title":"Cell"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1958","DOI":"10.3389\/fimmu.2019.01958","article-title":"Expression, Role, and Regulation of Neutrophil Fc\u03b3 Receptors","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"26733","DOI":"10.1074\/jbc.M202069200","article-title":"Lack of Fucose on Human IgG1 N-Linked Oligosaccharide Improves Binding to Human Fc\u03b3RIII and Antibody-dependent Cellular Toxicity","volume":"277","author":"Shields","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.molimm.2020.03.010","article-title":"Glycosylation of Fc\u03b3 receptors influences their interaction with various IgG1 glycoforms","volume":"121","author":"Cambay","year":"2020","journal-title":"Mol. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"11957","DOI":"10.1038\/s41598-019-48323-w","article-title":"The Fab portion of immunoglobulin G contributes to its binding to Fc\u03b3 receptor III","volume":"9","author":"Yogo","year":"2019","journal-title":"Sci. Rep."}],"container-title":["Biomedicines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9059\/11\/11\/2890\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:11:37Z","timestamp":1760130697000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9059\/11\/11\/2890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,25]]},"references-count":69,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["biomedicines11112890"],"URL":"https:\/\/doi.org\/10.3390\/biomedicines11112890","relation":{},"ISSN":["2227-9059"],"issn-type":[{"value":"2227-9059","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,25]]}}}