{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T10:11:49Z","timestamp":1778580709827,"version":"3.51.4"},"reference-count":119,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U23A20270"],"award-info":[{"award-number":["U23A20270"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Chinese hamster ovary (CHO) cells are commonly used to produce recombinant therapeutic proteins (RTPs). The yield of RTPs in CHO cells has been greatly improved through cell editing and optimization of culture media, cell culture processes, and expression vectors. However, the heterogeneity of cell clones and product aggregation considerably affect the yield and quality of RTPs. Recently, novel technologies such as semi-targeted and site-specific transgene integration, endoplasmic reticulum-residents, and cell culture process optimization have been used to address these issues. In this review, novel developments in the field of CHO cell expression system heterogeneity are summarized. Moreover, the advantages and limitations of the new strategies are discussed, and important methods for the control of RTP quality are outlined.<\/jats:p>","DOI":"10.3390\/ijms26031324","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T10:57:53Z","timestamp":1738666673000},"page":"1324","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["From Cell Clones to Recombinant Protein Product Heterogeneity in Chinese Hamster Ovary Cell Systems"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6920-208X","authenticated-orcid":false,"given":"Chong","family":"Wang","sequence":"first","affiliation":[{"name":"School of Medical Engineering, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China"},{"name":"International Joint Laboratory of Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Wang","sequence":"additional","affiliation":[{"name":"International Joint Laboratory of Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia-Xin","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Science and Technology, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0793-1006","authenticated-orcid":false,"given":"Tian-Yun","family":"Wang","sequence":"additional","affiliation":[{"name":"International Joint Laboratory of Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang Medical University, Xinxiang 453003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1038\/s41587-022-01582-x","article-title":"Biopharmaceutical benchmarks 2022","volume":"40","author":"Walsh","year":"2022","journal-title":"Nat. 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