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Thus, the development of an HCV vaccine is of great importance. Prior work has developed candidate vaccines, including more potent glycoengineered viral proteins and secreted forms of the E1E2 envelope heterodimer (sE1E2). However, efforts to express them recombinantly in Chinese hamster ovary (CHO) cells have resulted in very low titers. To address this challenge, here we employed a multi\u2010omics approach to identify protein interactors that may enhance the secretion of an sE1E2 vaccine candidate. We detected protein\u2010protein interactions (PPIs) using the Biotinylation by Antibody Recognition (BAR) assay and integrated these data with RNA\u2010Seq. Through this, we identified and overexpressed proteins that interact with sE1E2 in CHO cells. Among these, CUL4A and YWHAH enhanced sE1E2 secretion in our glycoengineered CHO cells. The integration of omics techniques and genetic engineering in this study provides valuable insights into the host cell proteins that interact with the HCV E1E2 heterodimer, and how they may be harnessed to improve protein secretion in CHO cells to enable more affordable and accessible biotherapeutics.<\/jats:p>","DOI":"10.1002\/biot.70112","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T10:03:59Z","timestamp":1756893839000},"source":"Crossref","is-referenced-by-count":6,"title":["Enhanced Production of HCV E1E2 Subunit Vaccine Candidates via Protein\u2010Protein Interaction Identification in Glycoengineered CHO Cells"],"prefix":"10.1002","volume":"20","author":[{"given":"Mina Ying Min","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Bioengineering University of California, San Diego  La Jolla California USA"},{"name":"Center for Molecular Medicine University of Georgia  Athens Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Rocamora","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caressa M.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of California, San Diego  La Jolla California USA"},{"name":"Department of Pediatrics University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seunghyeon","family":"Shin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of California, San Diego  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Maurya","sequence":"additional","affiliation":[{"name":"Sanford Burnham Prebys Medical Discovery Institute  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric A.","family":"Toth","sequence":"additional","affiliation":[{"name":"Institute for Bioscience and Biotechnology Research University of Maryland  Rockville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"Fuerst","sequence":"additional","affiliation":[{"name":"Institute for Bioscience and Biotechnology Research University of Maryland  Rockville Maryland USA"},{"name":"Department of Cell Biology and Molecular Genetics University of Maryland  College Park Maryland USA"},{"name":"NeuImmune, Inc.  Sykesville Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7700-3654","authenticated-orcid":false,"given":"Nathan E.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of California, San Diego  La Jolla California USA"},{"name":"Center for Molecular Medicine University of Georgia  Athens Georgia USA"},{"name":"Department of Pediatrics University of California, San Diego  La Jolla California USA"},{"name":"Complex Carbohydrate Research Center and Department of Biochemistry and Molecular Biology University of Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v7.i14.1843"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.6"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines8010090"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13050837"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz076"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abn9884"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13061027"},{"issue":"2","key":"e_1_2_9_9_1","first-page":"71","article-title":"Assembly of a Functional HCV Glycoprotein Heterodimer","volume":"9","author":"Lavie M.","year":"2007","journal-title":"Current Issues in Molecular Biology"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2022.09.057"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.00452\u201016"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2023.108206"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01656\u201018"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41541\u2010025\u201001161\u20106"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2015149118"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201039659\u2010z"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2112008119"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.2474"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/v16050803"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI160058"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI130720"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2010.06.084"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.06.029"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01552\u201016"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00704\u201020"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2025.07.006"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4533"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2023.12.006"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2016.09.004"},{"key":"e_1_2_9_30_1","first-page":"237","volume-title":"Chapter 11\u2014Proximity Labeling for Investigating Protein\u2010protein Interactions","author":"Pfeiffer C. 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