{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T16:49:10Z","timestamp":1789836550768,"version":"4.0.1"},"reference-count":159,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T00:00:00Z","timestamp":1753401600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"US National Science Foundation: Industry-University Cooperative Research Center","award":["NSF-1624641"],"award-info":[{"award-number":["NSF-1624641"]}]},{"name":"US National Science Foundation: Industry-University Cooperative Research Center","award":["P200A180076"],"award-info":[{"award-number":["P200A180076"]}]},{"name":"Department of Education","award":["NSF-1624641"],"award-info":[{"award-number":["NSF-1624641"]}]},{"name":"Department of Education","award":["P200A180076"],"award-info":[{"award-number":["P200A180076"]}]},{"name":"Clemson University Creative Inquiry program","award":["NSF-1624641"],"award-info":[{"award-number":["NSF-1624641"]}]},{"name":"Clemson University Creative Inquiry program","award":["P200A180076"],"award-info":[{"award-number":["P200A180076"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chinese hamster ovary (CHO) cells are the most common protein production platform for glycosylated biopharmaceuticals due to their relatively efficient secretion systems, post-translational modification (PTM) machinery, and quality control mechanisms. However, high productivity and titer demands can overburden these processes. In particular, the endoplasmic reticulum (ER) can become overwhelmed with misfolded proteins, triggering the unfolded protein response (UPR) as evidence of ER stress. The UPR increases the expression of multiple genes\/proteins, which are beneficial to protein folding and secretion. However, if the stressed ER cannot return to a state of homeostasis, a prolonged UPR results in apoptosis. Because ER stress poses a substantial bottleneck for secreting protein therapeutics, CHO cells are both selected for and engineered to improve high-quality protein production through optimized UPR and ER stress management. This is vital for optimizing industrial CHO cell fermentation. This review begins with an overview of common ER-stress related markers. Next, the optimal UPR profile of high-producing CHO cells is discussed followed by the context-dependency of a UPR profile for any given recombinant CHO cell line. Recent efforts to control and engineer ER stress-related responses in CHO cell lines through the use of various bioprocess operations and activation\/inhibition strategies are elucidated. Finally, this review concludes with a discussion on future directions for engineering the CHO cell UPR.<\/jats:p>","DOI":"10.3390\/ijms26157189","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T11:38:41Z","timestamp":1753443521000},"page":"7189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Recent Advances in Engineering the Unfolded Protein Response in Recombinant Chinese Hamster Ovary Cell Lines"],"prefix":"10.3390","volume":"26","author":[{"given":"Dyllan","family":"Rives","sequence":"first","affiliation":[{"name":"Department of Chemical & Biomolecular Engineering, Clemson University, 206 S. Palmetto Blvd., Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tara","family":"Richbourg","sequence":"additional","affiliation":[{"name":"Department of Chemical & Biomolecular Engineering, Clemson University, 206 S. Palmetto Blvd., Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sierra","family":"Gurtler","sequence":"additional","affiliation":[{"name":"Department of Chemical & Biomolecular Engineering, Clemson University, 206 S. Palmetto Blvd., Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Martone","sequence":"additional","affiliation":[{"name":"Department of Chemical & Biomolecular Engineering, Clemson University, 206 S. Palmetto Blvd., Clemson, SC 29634, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9274-3749","authenticated-orcid":false,"given":"Mark A.","family":"Blenner","sequence":"additional","affiliation":[{"name":"Department of Chemical & Biomolecular Engineering, Clemson University, 206 S. Palmetto Blvd., Clemson, SC 29634, USA"},{"name":"Department of Chemical & Biomolecular Engineering, University of Delaware, 590 Avenue 1743, Newark, DE 19713, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,25]]},"reference":[{"key":"ref_1","unstructured":"(2025, May 17). Monoclonal Antibodies Market Size Set to Hit USD 679.03 Bn by 2033. Available online: https:\/\/www.visionresearchreports.com\/monoclonal-antibodies-market\/38040."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gupta, S.K., Srivastava, S.K., Sharma, A., Nalage, V.H.H., Salvi, D., Kushwaha, H., Chitnis, N.B., and Shukla, P. (2017). Metabolic Engineering of CHO Cells for the Development of a Robust Protein Production Platform. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181455"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.copbio.2014.06.010","article-title":"The Choice of Mammalian Cell Host and Possibilities for Glycosylation Engineering","volume":"30","author":"Butler","year":"2014","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.jbiosc.2015.01.002","article-title":"Optimization of Cell Line Development in the GS-CHO Expression System Using a High-Throughput, Single Cell-Based Clone Selection System","volume":"120","author":"Nakamura","year":"2015","journal-title":"J. Biosci. Bioeng."},{"key":"ref_5","unstructured":"(2025, May 17). FDALabel, Available online: https:\/\/nctr-crs.fda.gov\/fdalabel\/ui\/search."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/B978-0-12-385114-7.00004-0","article-title":"Measuring ER Stress and the Unfolded Protein Response Using Mammalian Tissue Culture System","volume":"490","author":"Oslowski","year":"2011","journal-title":"Methods in Enzymology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/B978-0-12-385928-0.00011-0","article-title":"Monitoring and Manipulating Mammalian Unfolded Protein Response","volume":"491","author":"Hiramatsu","year":"2011","journal-title":"Methods in Enzymology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/febs.15107","article-title":"A Guide to Assessing Endoplasmic Reticulum Homeostasis and Stress in Mammalian Systems","volume":"287","author":"Sicari","year":"2020","journal-title":"FEBS J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1080\/07388551.2022.2047004","article-title":"The Secretory Pathway\u2014The Key for Unlocking the Potential of Chinese Hamster Ovary Cell Factories for Manufacturing Therapeutic Proteins","volume":"43","author":"Torres","year":"2023","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1007\/s10529-014-1537-y","article-title":"The Endoplasmic Reticulum and Unfolded Protein Response in the Control of Mammalian Recombinant Protein Production","volume":"36","author":"Hussain","year":"2014","journal-title":"Biotechnol. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.copbio.2018.01.007","article-title":"Debottlenecking Protein Secretion and Reducing Protein Aggregation in the Cellular Host","volume":"53","author":"Zhou","year":"2018","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1002\/bit.27247","article-title":"Oxidative Stress-alleviating Strategies to Improve Recombinant Protein Production in CHO Cells","volume":"117","author":"Chevallier","year":"2020","journal-title":"Biotechnol. Bioengr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1080\/07388551.2019.1605496","article-title":"Transcription Factor Engineering in CHO Cells for Recombinant Protein Production","volume":"39","author":"Latorre","year":"2019","journal-title":"Crit. Rev. Biotechnol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.biotechadv.2016.11.008","article-title":"Improving the Secretory Capacity of Chinese Hamster Ovary Cells by Ectopic Expression of Effector Genes: Lessons Learned and Future Directions","volume":"35","author":"Hansen","year":"2017","journal-title":"Biotechnol. Adv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.bej.2018.04.008","article-title":"Biochemical and Metabolic Engineering Approaches to Enhance Production of Therapeutic Proteins in Animal Cell Cultures","volume":"136","author":"Templeton","year":"2018","journal-title":"Biochem. Eng. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1002\/bit.27269","article-title":"Attenuating Apoptosis in Chinese Hamster Ovary Cells for Improved Biopharmaceutical Production","volume":"117","author":"Henry","year":"2020","journal-title":"Biotechnol. Bioengr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jbiotec.2024.06.005","article-title":"Molecular Biomarkers Identification and Applications in CHO Bioprocessing","volume":"392","author":"Desmurget","year":"2024","journal-title":"J. Biotechnol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1002\/bit.25957","article-title":"Proteomic Differences in Recombinant CHO Cells Producing Two Similar Antibody Fragments","volume":"113","author":"Sommeregger","year":"2016","journal-title":"Biotechnol. Bioeng."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ymben.2012.12.003","article-title":"CHO Cell Engineering to Prevent Polypeptide Aggregation and Improve Therapeutic Protein Secretion","volume":"21","author":"Girod","year":"2014","journal-title":"Metab. Eng."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.1242\/jcs.204396","article-title":"Targeting and Translocation of Proteins to the Endoplasmic Reticulum at a Glance","volume":"130","author":"Aviram","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.freeradbiomed.2017.03.031","article-title":"The Endoplasmic Reticulum: A Hub of Protein Quality Control in Health and Disease","volume":"108","author":"Hipp","year":"2017","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.tibs.2018.06.005","article-title":"Quality Control in the Endoplasmic Reticulum: Crosstalk between ERAD and UPR Pathways","volume":"43","author":"Hwang","year":"2018","journal-title":"Trends Biochem. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.molcel.2017.06.017","article-title":"The Unfolded Protein Response and Cell Fate Control","volume":"69","author":"Hetz","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s10616-013-9678-8","article-title":"Dynamics of Unfolded Protein Response in Recombinant CHO Cells","volume":"67","author":"Prashad","year":"2015","journal-title":"Cytotechnology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1111\/boc.201100055","article-title":"The Unfolded Protein Response at the Crossroads of Cellular Life and Death during Endoplasmic Reticulum Stress","volume":"104","author":"Bertrand","year":"2012","journal-title":"Biol. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1002\/j.1460-2075.1992.tb05201.x","article-title":"Overexpression of GRP78 Mitigates Stress Induction of Glucose Regulated Proteins and Blocks Secretion of Selective Proteins in Chinese Hamster Ovary Cells","volume":"11","author":"Dorner","year":"1992","journal-title":"EMBO J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1002\/bit.26263","article-title":"ATF6\u03b2-based Fine-tuning of the Unfolded Protein Response Enhances Therapeutic Antibody Productivity of Chinese Hamster Ovary Cells","volume":"114","author":"Pieper","year":"2017","journal-title":"Biotechnol. Bioeng."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"22865","DOI":"10.1074\/jbc.M701213200","article-title":"Effects of the Isoform-Specific Characteristics of ATF6\u03b1 and ATF6\u03b2 on Endoplasmic Reticulum Stress Response Gene Expression and Cell Viability","volume":"282","author":"Thuerauf","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"9199","DOI":"10.1074\/jbc.M010486200","article-title":"Identification of ERSE-II, a New Cis-Acting Element Responsible for the ATF6-Dependent Mammalian Unfolded Protein Response","volume":"276","author":"Kokame","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"33741","DOI":"10.1074\/jbc.273.50.33741","article-title":"Identification of the Cis-Acting Endoplasmic Reticulum Stress Response Element Responsible for Transcriptional Induction of Mammalian Glucose-Regulated Proteins","volume":"273","author":"Yoshida","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6755","DOI":"10.1128\/MCB.20.18.6755-6767.2000","article-title":"ATF6 Activated by Proteolysis Binds in the Presence of NF-Y (CBF) Directly to the Cis -Acting Element Responsible for the Mammalian Unfolded Protein Response","volume":"20","author":"Yoshida","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0092-8674(01)00611-0","article-title":"XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription Factor","volume":"107","author":"Yoshida","year":"2001","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Hillary, R.F., and FitzGerald, U. (2018). A Lifetime of Stress: ATF6 in Development and Homeostasis. J. Biomed. Sci., 25.","DOI":"10.1186\/s12929-018-0453-1"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1247\/csf.07044","article-title":"ATF6 Is a Transcription Factor Specializing in the Regulation of Quality Control Proteins in the Endoplasmic Reticulum","volume":"33","author":"Adachi","year":"2008","journal-title":"Cell Struct. Funct."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1093\/jb\/mvh122","article-title":"Differential Contributions of ATF6 and XBP1 to the Activation of Endoplasmic Reticulum Stress-Responsive Cis-Acting Elements ERSE, UPRE and ERSE-II","volume":"136","author":"Yamamoto","year":"2004","journal-title":"J. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.devcel.2007.07.018","article-title":"Transcriptional Induction of Mammalian ER Quality Control Proteins Is Mediated by Single or Combined Action of ATF6\u03b1 and XBP1","volume":"13","author":"Yamamoto","year":"2007","journal-title":"Dev. Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1016\/j.tcb.2013.06.005","article-title":"IRE1: ER Stress Sensor and Cell Fate Executor","volume":"23","author":"Chen","year":"2013","journal-title":"Trends Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7448","DOI":"10.1128\/MCB.23.21.7448-7459.2003","article-title":"XBP-1 Regulates a Subset of Endoplasmic Reticulum Resident Chaperone Genes in the Unfolded Protein Response","volume":"23","author":"Lee","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1016\/j.celrep.2013.03.024","article-title":"Stress-Independent Activation of XBP1s and\/or ATF6 Reveals Three Functionally Diverse ER Proteostasis Environments","volume":"3","author":"Shoulders","year":"2013","journal-title":"Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1242\/jcs.045625","article-title":"ATF6\u03b1 Induces XBP1-Independent Expansion of the Endoplasmic Reticulum","volume":"122","author":"Bommiasamy","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1089\/ars.2006.8.1391","article-title":"The Endoplasmic Reticulum: Folding, Calcium Homeostasis, Signaling, and Redox Control","volume":"8","author":"Klappa","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Romine, I.C., and Wiseman, R.L. (2019). PERK Signaling Regulates Extracellular Proteostasis of an Amyloidogenic Protein During Endoplasmic Reticulum Stress. Sci. Rep., 9.","DOI":"10.1038\/s41598-018-37207-0"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"9557","DOI":"10.1093\/nar\/gks762","article-title":"Translation Termination Efficiency Modulates ATF4 Response by Regulating ATF4 mRNA Translation at 5\u2032 Short ORFs","volume":"40","author":"Jolles","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S1097-2765(03)00105-9","article-title":"An Integrated Stress Response Regulates Amino Acid Metabolism and Resistance to Oxidative Stress","volume":"11","author":"Harding","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1194\/jlr.R067595","article-title":"The Role of ER Stress in Lipid Metabolism and Lipotoxicity","volume":"57","author":"Han","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Coelho, D.S., and Domingos, P.M. (2014). Physiological Roles of Regulated Ire1 Dependent Decay. Front. Genet., 5.","DOI":"10.3389\/fgene.2014.00076"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1002\/biot.201400857","article-title":"Microarray Profiling of Preselected CHO Host Cell Subclones Identifies Gene Expression Patterns Associated with In-creased Production Capacity","volume":"10","author":"Harreither","year":"2015","journal-title":"Biotechnol. J."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Lund, A.M., Kaas, C.S., Brandl, J., Pedersen, L.E., Kildegaard, H.F., Kristensen, C., and Andersen, M.R. (2017). Network Reconstruction of the Mouse Secretory Pathway Applied on CHO Cell Transcriptome Data. BMC Syst. Biol., 11.","DOI":"10.1186\/s12918-017-0414-4"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s10616-014-9693-4","article-title":"Evaluating the Bottlenecks of Recombinant IgM Production in Mammalian Cells","volume":"67","author":"Chromikova","year":"2015","journal-title":"Cytotechnology"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Sebasti\u00e3o, M.J., Hoffman, M., Escandell, J., Tousi, F., Zhang, J., Figueroa, B., DeMaria, C., and Gomes-Alves, P. (2023). Identification of Mispairing Omic Signatures in Chinese Hamster Ovary (CHO) Cells Producing a Tri-Specific Antibody. Biomedicines, 11.","DOI":"10.3390\/biomedicines11112890"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Talbot, N.E., Mead, E.J., Davies, S.A., Uddin, S., and Smales, C.M. (2019). Application of ER Stress Biomarkers to Predict Formulated Monoclonal Antibody Stability. Biotechnol. J., 14.","DOI":"10.1002\/biot.201900024"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/bit.27196","article-title":"Unraveling What Makes a Monoclonal Antibody Difficult-to-express: From Intracellular Accumulation to Incomplete Folding and Degradation via ERAD","volume":"117","author":"Mathias","year":"2020","journal-title":"Biotechnol. Bioeng."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Tang, D., Sandoval, W., Lam, C., Haley, B., Liu, P., Xue, D., Roy, D., Patapoff, T., Louie, S., and Snedecor, B. (2020). UBR E3 Ligases and the PDIA3 Protease Control Degradation of Unfolded Antibody Heavy Chain by ERAD. J. Cell Biol., 219.","DOI":"10.1083\/jcb.201908087"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Sulaj, E., Schwaigerlehner, L., Sandell, F.L., Dohm, J.C., Marzban, G., and Kunert, R. (2024). Quantitative Proteomics Reveals Cellular Responses to Individual mAb Expression and Tunicamycin in CHO Cells. Appl. Microbiol. Biotechnol., 108.","DOI":"10.1007\/s00253-024-13223-1"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3197","DOI":"10.1007\/s00216-018-1029-3","article-title":"Multiple Reaction Monitoring Targeted LC-MS Analysis of Potential Cell Death Marker Proteins for Increased Bioprocess Control","volume":"410","author":"Albrecht","year":"2018","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1963094","DOI":"10.1080\/19420862.2021.1963094","article-title":"Untargeted Proteomics Reveals Upregulation of Stress Response Pathways during CHO-Based Monoclonal Antibody Manufacturing Process Leading to Disulfide Bond Reduction","volume":"13","author":"Park","year":"2021","journal-title":"mAbs"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"100278","DOI":"10.1016\/j.mcpro.2022.100278","article-title":"Spatial Proteomics Reveals Differences in the Cellular Architecture of Antibody-Producing CHO and Plasma Cell\u2013Derived Cells","volume":"21","author":"Kretz","year":"2022","journal-title":"Mol. Cell. Proteom."},{"key":"ref_60","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_61","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1002\/btpr.1534","article-title":"Analysis of Dynamic Changes in the Proteome of a Bcl-XL Overexpressing Chinese Hamster Ovary Cell Culture during Exponential and Stationary Phases","volume":"28","author":"Carlage","year":"2012","journal-title":"Biotechnol. Prog."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Tung, M., Tang, D., Wang, S., Zhan, D., Kiplinger, K., Pan, S., Jing, Y., Shen, A., Ahyow, P., and Snedecor, B. (2018). High Intracellular Seed Train BiP Levels Correlate With Poor Production Culture Performance in CHO Cells. Biotechnol. J., 13.","DOI":"10.1002\/biot.201700746"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jbiotec.2017.11.008","article-title":"Proteomic Analysis of CHO Cell Lines Producing High and Low Quantities of a Recombinant Antibody before and after Selection with Methotrexate","volume":"265","author":"Hausmann","year":"2018","journal-title":"J. Biotechnol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"104074","DOI":"10.1016\/j.isci.2022.104074","article-title":"Chromosomal Instability Drives Convergent and Divergent Evolution toward Advantageous Inherited Traits in Mammalian CHO Bioproduction Lineages","volume":"25","author":"Huhn","year":"2022","journal-title":"iScience"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"12439","DOI":"10.1021\/acsomega.0c06030","article-title":"Compartmentalized Proteomic Profiling Outlines the Crucial Role of the Classical Secretory Pathway during Recombinant Protein Production in Chinese Hamster Ovary Cells","volume":"6","author":"Wulff","year":"2021","journal-title":"ACS Omega"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2020081","DOI":"10.1080\/19420862.2021.2020081","article-title":"Mitochondrial Membrane Potential-Enriched CHO Host: A Novel and Powerful Tool for Improving Biomanufacturing Capability","volume":"14","author":"Chakrabarti","year":"2022","journal-title":"mAbs"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Avello, V., Torres, M., Vergara, M., Berrios, J., Valdez-Cruz, N.A., Acevedo, C., Molina Sampayo, M., Dickson, A.J., and Altamirano, C. (2022). Enhanced Recombinant Protein Production in CHO Cell Continuous Cultures under Growth-Inhibiting Conditions Is Associated with an Arrested Cell Cycle in G1\/G0 Phase. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0277620"},{"key":"ref_68","unstructured":"Kaas, C.S. (2015). Characterization of Chinese Hamster Ovary Cells Producing Coagulation Factor VIII Using Multi-Omics Tools. [Ph.D. Thesis, Technical University of Denmark]."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Orlova, N.A., Kovnir, S.V., Gabibov, A.G., and Vorobiev, I.I. (2017). Stable High-Level Expression of Factor VIII in Chinese Hamster Ovary Cells in Improved Elongation Factor-1 Alpha-Based System. BMC Biotechnol., 17.","DOI":"10.1186\/s12896-017-0353-6"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1248\/bpb.b15-00618","article-title":"Endoplasmic Reticulum Stress Response and Mutant Protein Degradation in CHO Cells Accumulating Antithrombin (C95R) in Russell Bodies","volume":"38","author":"Kimura","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1248\/bpb.b14-00773","article-title":"Characterization of Russell Bodies Accumulating Mutant Antithrombin Derived from the Endoplasmic Reticulum","volume":"38","author":"Kimura","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Maldonado-Agurto, R., and Dickson, A.J. (2018). Multiplexed Digital mRNA Expression Analysis Profiles System-Wide Changes in mRNA Abundance and Responsiveness of UPR-Specific Gene Expression Changes During Batch Culture of Recombinant Chinese Hamster Ovary Cells. Biotechnol. J., 13.","DOI":"10.1002\/biot.201700429"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Coats, M.T., Bydlinski, N., Maresch, D., Diendorfer, A., Klanert, G., and Borth, N. (2020). mRNA Transfection into CHO-Cells Reveals Production Bottlenecks. Biotechnol. J., 15.","DOI":"10.1002\/biot.201900198"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jbiotec.2019.03.009","article-title":"Reducing Recombinant Protein Expression during CHO Pool Selection Enhances Frequency of High-Producing Cells","volume":"296","author":"Poulain","year":"2019","journal-title":"J. Biotechnol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Sinharoy, P., Aziz, A.H., Majewska, N.I., Ahuja, S., and Handlogten, M.W. (2020). Perfusion Reduces Bispecific Antibody Aggregation via Mitigating Mitochondrial Dysfunction-Induced Glutathione Oxidation and ER Stress in CHO Cells. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-73573-4"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/bit.28866","article-title":"Elevated Endoplasmic Reticulum pH Is Associated with High Growth and bisAb Aggregation in CHO Cells","volume":"122","author":"McFarland","year":"2025","journal-title":"Biotechnol. Bioeng."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/bit.21562","article-title":"Effects of Overexpression of X-box Binding Protein 1 on Recombinant Protein Production in Chinese Hamster Ovary and NS0 Myeloma Cells","volume":"99","author":"Ku","year":"2008","journal-title":"Biotechnol. Bioeng."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.jbiotec.2020.02.008","article-title":"Enhancing Titers and Productivity of rCHO Clones with a Combination of an Optimized Fed-Batch Process and ER-Stress Adaptation","volume":"311","author":"Chandrawanshi","year":"2020","journal-title":"J. Biotechnol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1007\/s00253-022-11861-x","article-title":"Hyperosmolality in CHO Cell Culture: Effects on the Proteome","volume":"106","author":"Romanova","year":"2022","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1002\/btpr.2090","article-title":"A Quantitative Proteomic Analysis of Cellular Responses to High Glucose Media in Chinese Hamster Ovary Cells","volume":"31","author":"Liu","year":"2015","journal-title":"Biotechnol. Prog."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Ali, A.S., Raju, R., Kshirsagar, R., Ivanov, A.R., Gilbert, A., Zang, L., and Karger, B.L. (2019). Multi-Omics Study on the Impact of Cysteine Feed Level on Cell Viability and mAb Production in a CHO Bioprocess. Biotechnol. J., 14.","DOI":"10.1002\/biot.201800352"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Ali, A.S., Chen, R., Raju, R., Kshirsagar, R., Gilbert, A., Zang, L., Karger, B.L., and Ivanov, A.R. (2020). Multi-Omics Reveals Impact of Cysteine Feed Concentration and Resulting Redox Imbalance on Cellular Energy Metabolism and Specific Productivity in CHO Cell Bioprocessing. Biotechnol. J., 15.","DOI":"10.1002\/biot.201900565"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Komuczki, D., Stadermann, A., Bentele, M., Unsoeld, A., Grillari, J., Mueller, M.M., Paul, A., and Fischer, S. (2022). High Cysteine Concentrations in Cell Culture Media Lead to Oxidative Stress and Reduced Bioprocess Performance of Recombinant CHO Cells. Biotechnol. J., 17.","DOI":"10.1002\/biot.202200029"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1002\/bit.26460","article-title":"Intracellular Response to Process Optimization and Impact on Productivity and Product Aggregates for a High-titer CHO Cell Process","volume":"115","author":"Handlogten","year":"2018","journal-title":"Biotechnol. Bioeng."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/bit.28000","article-title":"Combined Gene and Environmental Engineering Offers a Synergetic Strategy to Enhance R-protein Production in Chinese Hamster Ovary Cells","volume":"119","author":"Torres","year":"2022","journal-title":"Biotechnol. Bioeng."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s00449-024-02987-5","article-title":"Synergistic Promotion of Transient Transgene Expression in CHO Cells by PDI\/XBP-1s Co-Transfection and Mild Hypothermia","volume":"47","author":"Zhang","year":"2024","journal-title":"Bioprocess. Biosyst. Eng."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Latorre, Y., Torres, M., Vergara, M., Berrios, J., Sampayo, M.M., G\u00f6decke, N., Wirth, D., Hauser, H., Dickson, A.J., and Altamirano, C. (2023). Engineering of Chinese Hamster Ovary Cells for Co-Overexpressing MYC and XBP1s Increased Cell Proliferation and Recombinant EPO Production. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-28622-z"},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Gulis, G., Simi, K.C.R., De Toledo, R.R., Maranhao, A.Q., and Brigido, M.M. (2014). Optimization of Heterologous Protein Production in Chinese Hamster Ovary Cells under Overexpression of Spliced Form of Human X-Box Binding Protein. BMC Biotechnol., 14.","DOI":"10.1186\/1472-6750-14-26"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"8429","DOI":"10.1007\/s00253-015-6789-5","article-title":"Understanding the Intracellular Effects of Yeast Extract on the Enhancement of Fc-Fusion Protein Production in Chinese Hamster Ovary Cell Culture","volume":"99","author":"Hu","year":"2015","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Bedoya-L\u00f3pez, A., Estrada, K., Sanchez-Flores, A., Ram\u00edrez, O.T., Altamirano, C., Segovia, L., Miranda-R\u00edos, J., Trujillo-Rold\u00e1n, M.A., and Valdez-Cruz, N.A. (2016). Effect of Temperature Downshift on the Transcriptomic Responses of Chinese Hamster Ovary Cells Using Recombinant Human Tissue Plasminogen Activator Production Culture. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0151529"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Torres, M., Z\u00fa\u00f1iga, R., Gutierrez, M., Vergara, M., Collazo, N., Reyes, J., Berrios, J., Aguillon, J.C., Molina, M.C., and Altamirano, C. (2018). Mild Hypothermia Upregulates Myc and Xbp1s Expression and Improves Anti-TNF\u03b1 Production in CHO Cells. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0194510"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Torres, M., Akhtar, S., McKenzie, E.A., and Dickson, A.J. (2021). Temperature Down-Shift Modifies Expression of UPR-\/ERAD-Related Genes and Enhances Production of a Chimeric Fusion Protein in CHO Cells. Biotechnol. J., 16.","DOI":"10.1002\/biot.202000081"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1002\/bit.20717","article-title":"Initial Transcriptome and Proteome Analyses of Low Culture Temperature-induced Expression in CHO Cells Producing Erythropoietin","volume":"93","author":"Baik","year":"2006","journal-title":"Biotechnol. Bioeng."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"570","DOI":"10.2174\/0929866525666180530121317","article-title":"The Effect of Culture Temperature on the Aggregation of Recombinant TNFR-Fc Is Regulated by the PERK-eIF2a Pathway in CHO Cells","volume":"25","author":"Wang","year":"2018","journal-title":"Protein Peptide Lett."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jbiotec.2018.09.007","article-title":"Characterization of Cellular States of CHO-K1 Suspension Cell Culture through Cell Cycle and RNA-Sequencing Profiling","volume":"286","author":"Tossolini","year":"2018","journal-title":"J. Biotechnol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1002\/bit.26777","article-title":"Untangling the Mechanism of 3-methyladenine in Enhancing the Specific Productivity: Transcriptome Analysis of Recombinant Chinese Hamster Ovary Cells Treated with 3-methyladenine","volume":"115","author":"Baek","year":"2018","journal-title":"Biotechnol. Bioeng."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Ha, T.K., Hansen, A.H., Kol, S., Kildegaard, H.F., and Lee, G.M. (2018). Baicalein Reduces Oxidative Stress in CHO Cell Cultures and Improves Recombinant Antibody Productivity. Biotechnol. J., 13.","DOI":"10.1002\/biot.201700425"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Ha, T.K., Hansen, A.H., Kildegaard, H.F., and Lee, G.M. (2019). BiP Inducer X: An ER Stress Inhibitor for Enhancing Recombinant Antibody Production in CHO Cell Culture. Biotechnol. J., 14.","DOI":"10.1002\/biot.201900130"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1002\/bit.25332","article-title":"Use of a Small Molecule Cell Cycle Inhibitor to Control Cell Growth and Improve Specific Productivity and Product Quality of Recombinant Proteins in CHO Cell Cultures","volume":"112","author":"Du","year":"2015","journal-title":"Biotechnol. Bioeng."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1002\/bit.28050","article-title":"Significant Impact of mTORC1 and ATF4 Pathways in CHO Cell Recombinant Protein Production Induced by CDK4\/6 Inhibitor","volume":"119","author":"Chang","year":"2022","journal-title":"Biotechnol. Bioeng."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Mao, L., Schneider, J.W., and Robinson, A.S. (2024). Rosmarinic Acid Enhances CHO Cell Productivity and Proliferation through Activation of the Unfolded Protein Response and the mTOR Pathway. Biotechnol. J., 19.","DOI":"10.1002\/biot.202300397"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Selvaprakash, K., Sideri, C., Henry, M., Efeoglu, E., Ryan, D., and Meleady, P. (2024). Characterization of the Ubiquitin-Modified Proteome of Recombinant Chinese Hamster Ovary Cells in Response to Endoplasmic Reticulum Stress. Biotechnol. J., 19.","DOI":"10.1002\/biot.202400413"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1080\/10826068.2018.1479865","article-title":"Using Chemical Chaperones to Increase Recombinant Human Erythropoietin Secretion in CHO Cell Line","volume":"49","author":"Mortazavi","year":"2019","journal-title":"Prep. Biochem. Biotechnol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1007\/s12257-024-00105-6","article-title":"Effect of 4-Phenylbutyrate Addition Timing on Titer of Fc-Fusion Protein in Chinese Hamster Ovary Cell Cultures","volume":"29","author":"Lim","year":"2024","journal-title":"Biotechnol. Bioprocess Eng."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s00253-020-10972-7","article-title":"Elucidating the Impact of Cottonseed Hydrolysates on CHO Cell Culture Performance through Transcriptomic Analysis","volume":"105","author":"Kumar","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.jbiosc.2017.05.005","article-title":"Activation of Unfolded Protein Response Pathway Is Important for Valproic Acid Mediated Increase in Immunoglobulin G Productivity in Recombinant Chinese Hamster Ovary Cells","volume":"124","author":"Segar","year":"2017","journal-title":"J. Biosci. Bioeng."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2560","DOI":"10.1002\/bit.26356","article-title":"Engineering CHO Cells with an Oncogenic KIT Improves Cells Growth, Resilience to Stress, and Productivity","volume":"114","author":"Mahameed","year":"2017","journal-title":"Biotechnol. Bioeng."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s12192-008-0054-0","article-title":"Calnexin Overexpression Sensitizes Recombinant CHO Cells to Apoptosis Induced by Sodium Butyrate Treatment","volume":"14","author":"Mohan","year":"2009","journal-title":"Cell Stress Chaperones"},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Ryan, D., Sideri, C.-K., Henry, M., Efeoglu, E., and Meleady, P. (2023). Label-Free Quantitative Proteomics Analysis of Producer and Non-Producer Chinese Hamsters Ovary (CHO) Cells under ER Stress Conditions. Curr. Res. Biotechnol., 6.","DOI":"10.1016\/j.crbiot.2023.100141"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jbiotec.2008.03.008","article-title":"An XBP-1 Dependent Bottle-Neck in Production of IgG Subtype Antibodies in Chemically Defined Serum-Free Chinese Hamster Ovary (CHO) Fed-Batch Processes","volume":"135","author":"Becker","year":"2008","journal-title":"J. Biotechnol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1002\/btpr.1693","article-title":"A CHO Cell Line Engineered to Express XBP1 and ERO1-L\u03b1 Has Increased Levels of Transient Protein Expression","volume":"29","author":"Cain","year":"2013","journal-title":"Biotechnol. Prog."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/bit.21758","article-title":"Improved Production of Recombinant Human Antithrombin III in Chinese Hamster Ovary Cells by ATF4 Overexpression","volume":"100","author":"Ohya","year":"2008","journal-title":"Biotechnol. Bioeng."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/s12033-008-9055-6","article-title":"Production of Recombinant Human Factor VIII in Different Cell Lines and the Effect of Human XBP1 Co-Expression","volume":"39","author":"Costa","year":"2008","journal-title":"Mol. Biotechnol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.4014\/jmb.1302.02035","article-title":"Engineering the Cellular Protein Secretory Pathway for Enhancement of Recombinant Tissue Plasminogen Activator Expression in Chinese Hamster Ovary Cells: Effects of CERT and XBP1s Genes","volume":"23","author":"Rahimpour","year":"2013","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_115","first-page":"6","article-title":"Development of Genetically Modified Chinese Hamster Ovary Host Cells for the Enhancement of Recombinant Tissue Plasminogen Activator Expression","volume":"23","author":"Rahimpour","year":"2016","journal-title":"Malays. J. Med. Sci."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.ymben.2024.03.007","article-title":"Nature as Blueprint: Global Phenotype Engineering of CHO Production Cells Based on a Multi-Omics Comparison with Plasma Cells","volume":"83","author":"Raab","year":"2024","journal-title":"Metab. Eng."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.ymben.2021.07.004","article-title":"Overexpression of Transcription Factor BLIMP1\/Prdm1 Leads to Growth Inhibition and Enhanced Secretory Capacity in Chinese Hamster Ovary Cells","volume":"67","author":"Torres","year":"2021","journal-title":"Metab. Eng."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.ymben.2021.12.004","article-title":"Reprogramming of Chinese Hamster Ovary Cells towards Enhanced Protein Secretion","volume":"69","author":"Torres","year":"2022","journal-title":"Metab. Eng."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.ymben.2021.11.001","article-title":"Improving the Secretory Capacity of CHO Producer Cells: The Effect of Controlled Blimp1 Expression, a Master Transcription Factor for Plasma Cells","volume":"69","author":"Kim","year":"2022","journal-title":"Metab. Eng."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.immuni.2004.06.010","article-title":"XBP1, Downstream of Blimp-1, Expands the Secretory Apparatus and Other Organelles, and Increases Protein Synthesis in Plasma Cell Differentiation","volume":"21","author":"Shaffer","year":"2004","journal-title":"Immunity"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Castellano, B.M., Tang, D., Marsters, S., Lam, C., Liu, P., Rose, C.M., Sandoval, W., Ashkenazi, A., Snedecor, B., and Misaghi, S. (2023). Activation of the PERK Branch of the Unfolded Protein Response during Production Reduces Specific Productivity in CHO Cells via Downregulation of PDGFRa and IRE1a Signaling. Biotechnol. Prog., 39.","DOI":"10.1002\/btpr.3354"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1002\/btpr.322","article-title":"Regulation of XBP-1 Signaling during Transient and Stable Recombinant Protein Production in CHO Cells","volume":"26","author":"Ku","year":"2010","journal-title":"Biotechnol. Prog."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.jbiotec.2009.11.018","article-title":"Evaluation of a Combinatorial Cell Engineering Approach to Overcome Apoptotic Effects in XBP-1(s) Expressing Cells","volume":"146","author":"Becker","year":"2010","journal-title":"J. Biotechnol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1002\/bit.27274","article-title":"Overexpression of Transcription Factor Foxa1 and Target Genes Remediate Therapeutic Protein Production Bottlenecks in Chinese Hamster Ovary Cells","volume":"117","author":"Berger","year":"2020","journal-title":"Biotechnol. Bioeng."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1021\/bp0498241","article-title":"Effect of Increased Expression of Protein Disulfide Isomerase and Heavy Chain Binding Protein on Antibody Secretion in a Recombinant CHO Cell Line","volume":"21","author":"Borth","year":"2008","journal-title":"Biotechnol. Prog."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1002\/bit.21453","article-title":"Effect of Doxycycline-regulated Protein Disulfide Isomerase Expression on the Specific Productivity of Recombinant CHO Cells: Thrombopoietin and Antibody","volume":"98","author":"Mohan","year":"2007","journal-title":"Biotechnol. Bioeng."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.jbiosc.2022.07.002","article-title":"Effect of Co-Overexpression of the Cargo Receptor ERGIC-53\/MCFD2 on Antibody Production and Intracellular IgG Secretion in Recombinant Chinese Hamster Ovary Cells","volume":"136","author":"Kirimoto","year":"2023","journal-title":"J. Biosci. Bioeng."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1007\/s00253-012-4365-9","article-title":"Overexpression of CHOP Alone and in Combination with Chaperones Is Effective in Improving Antibody Production in Mammalian Cells","volume":"97","author":"Nishimiya","year":"2013","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Zhang, C., Fu, Y., Zheng, W., Chang, F., Shen, Y., Niu, J., Wang, Y., and Ma, X. (2024). Enhancing the Antibody Production Efficiency of Chinese Hamster Ovary Cells through Improvement of Disulfide Bond Folding Ability and Apoptosis Resistance. Cells, 13.","DOI":"10.3390\/cells13171481"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.jbiotec.2020.02.012","article-title":"A Platform for Context-Specific Genetic Engineering of Recombinant Protein Production by CHO Cells","volume":"312","author":"Cartwright","year":"2020","journal-title":"J. Biotechnol."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Rives, D., Peak, C., and Blenner, M.A. (2024). RNASeq Highlights ATF6 Pathway Regulators for CHO Cell Engineering with Different Impacts of ATF6\u03b2 and WFS1 Knockdown on Fed-Batch Production of IgG1. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-64767-1"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1021\/bp000107q","article-title":"Effect of PDI Overexpression on Recombinant Protein Secretion in CHO Cells","volume":"16","author":"Davis","year":"2000","journal-title":"Biotechnol. Prog."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ymben.2020.02.001","article-title":"Engineered Transient and Stable Overexpression of Translation Factors eIF3i and eIF3c in CHOK1 and HEK293 Cells Gives Enhanced Cell Growth Associated with Increased C-Myc Expression and Increased Recombinant Protein Synthesis","volume":"59","author":"Roobol","year":"2020","journal-title":"Metab. Eng."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1007\/s10616-013-9631-x","article-title":"Improved Antibody Production in Chinese Hamster Ovary Cells by ATF4 Overexpression","volume":"65","author":"Haredy","year":"2013","journal-title":"Cytotechnology"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1002\/elsc.201500152","article-title":"Overexpression of GRP78 Enhances Survival of CHO Cells in Response to Serum Deprivation and Oxidative Stress","volume":"17","author":"Jiang","year":"2017","journal-title":"Eng. Life Sci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.jbiosc.2020.08.001","article-title":"Effect of the Disulfide Isomerase PDIa4 on the Antibody Production of Chinese Hamster Ovary Cells","volume":"130","author":"Komatsu","year":"2020","journal-title":"J. Biosci. Bioeng."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1263\/jbb.106.568","article-title":"Overexpression of GADD34 Enhances Production of Recombinant Human Antithrombin III in Chinese Hamster Ovary Cells","volume":"106","author":"Omasa","year":"2008","journal-title":"J. Biosci. Bioeng."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/bit.21917","article-title":"Enhancement of Transient Gene Expression and Culture Viability Using Chinese Hamster Ovary Cells Overexpressing Bcl-xL","volume":"101","author":"Majors","year":"2008","journal-title":"Biotechnol. Bioeng."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1007\/s10616-017-0170-8","article-title":"Enhanced IgG1 Production by Overexpression of Nuclear Factor Kappa B Inhibitor Zeta (NFKBIZ) in Chinese Hamster Ovary Cells","volume":"70","author":"Onitsuka","year":"2018","journal-title":"Cytotechnology"},{"key":"ref_140","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_141","doi-asserted-by":"crossref","first-page":"105217","DOI":"10.1016\/j.dib.2020.105217","article-title":"Data for Engineering Lipid Metabolism of Chinese Hamster Ovary (CHO) Cells for Enhanced Recombinant Protein Production","volume":"29","author":"Budge","year":"2020","journal-title":"Data Brief."},{"key":"ref_142","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_143","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.ymben.2006.01.006","article-title":"Xbp1-Based Engineering of Secretory Capacity Enhances the Productivity of Chinese Hamster Ovary Cells","volume":"8","author":"Tigges","year":"2006","journal-title":"Metab. Eng."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.nbt.2022.01.010","article-title":"Autophagy and Intracellular Product Degradation Genes Identified by Systems Biology Analysis Reduce Aggregation of Bispecific Antibody in CHO Cells","volume":"68","author":"Barzadd","year":"2022","journal-title":"New Biotechnol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1021\/bp025578m","article-title":"Effect of Doxycycline-Regulated ERp57 Expression on Specific Thrombopoietin Productivity of Recombinant CHO Cells","volume":"19","author":"Hwang","year":"2003","journal-title":"Biotechnol. Prog."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.ymben.2017.01.003","article-title":"Secretory Pathway Optimization of CHO Producer Cells by Co-Engineering of the mitosRNA-1978 Target Genes CerS2 and Tbc1D20","volume":"40","author":"Pieper","year":"2017","journal-title":"Metab. Eng."},{"key":"ref_147","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. Bioengr."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.ymben.2022.03.009","article-title":"Harnessing Secretory Pathway Differences between HEK293 and CHO to Rescue Production of Difficult to Express Proteins","volume":"72","author":"Malm","year":"2022","journal-title":"Metab. Eng."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1007\/s12257-011-0653-y","article-title":"A Role of GADD153 in ER Stress-Induced Apoptosis in Recombinant Chinese Hamster Ovary Cells","volume":"17","author":"Mohan","year":"2012","journal-title":"Biotechnol. Bioprocess Eng."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1002\/bit.26855","article-title":"Whole Synthetic Pathway Engineering of Recombinant Protein Production","volume":"116","author":"Brown","year":"2019","journal-title":"Biotechnol. Bioengr."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1007\/s10529-021-03153-7","article-title":"Differential Expression of miRNAs and Functional Role of Mir-200a in High and Low Productivity CHO Cells Expressing an Fc Fusion Protein","volume":"43","author":"Bryan","year":"2021","journal-title":"Biotechnol. Lett."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"100785","DOI":"10.1016\/j.isci.2019.100785","article-title":"Defining lncRNAs Correlated with CHO Cell Growth and IgG Productivity by RNA-Seq","volume":"23","author":"Vito","year":"2020","journal-title":"iScience"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jbiotec.2018.10.008","article-title":"Depletion of Endogenous miRNA-378-3p Increases Peak Cell Density of CHO DP12 Cells and Is Correlated with Elevated Levels of Ubiquitin Carboxyl-Terminal Hydrolase 14","volume":"288","author":"Costello","year":"2018","journal-title":"J. Biotechnol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2599","DOI":"10.1002\/bit.24527","article-title":"Development of a Novel ER Stress Based Selection System for the Isolation of Highly Productive Clones","volume":"109","author":"Kober","year":"2012","journal-title":"Biotechnol. Bioengr."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Tanemura, H., Masuda, K., Okumura, T., Takagi, E., Kajihara, D., Kakihara, H., Nonaka, K., and Ushioda, R. (2022). Development of a Stable Antibody Production System Utilizing an Hspa5 Promoter in CHO Cells. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-11342-1"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ymben.2022.02.002","article-title":"Endogenous BiP Reporter System for Simultaneous Identification of ER Stress and Antibody Production in Chinese Hamster Ovary Cells","volume":"72","author":"Kyeong","year":"2022","journal-title":"Metab. Eng."},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Roy, G., Zhang, S., Li, L., Higham, E., Wu, H., Marelli, M., and Bowen, M.A. (2017). Development of a Fluorescent Reporter System for Monitoring ER Stress in Chinese Hamster Ovary Cells and Its Application for Therapeutic Protein Production. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0183694"},{"key":"ref_158","unstructured":"Willmott, J.A. (2022). Developing Novel Biosensors for Monitoring Antibody Production in Chinese Hamster Ovary (CHO) Cells. [Ph.D. Thesis, University of Sheffield]."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1002\/bit.24877","article-title":"Non-invasive UPR Monitoring System and Its Applications in CHO Production Cultures","volume":"110","author":"Du","year":"2013","journal-title":"Biotechnol. 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