From Cell Clones to Recombinant Protein Product Heterogeneity in Chinese Hamster Ovary Cell Systems

被引:1
作者
Wang, Chong [1 ]
Guo, Xiao [2 ,3 ]
Wang, Wen [3 ]
Li, Jia-Xin [2 ]
Wang, Tian-Yun [3 ]
机构
[1] Xinxiang Med Univ, Sch Med Engn, Xinxiang 453003, Peoples R China
[2] Xinxiang Med Univ, Sch Life Sci & Technol, Xinxiang 453003, Peoples R China
[3] Xinxiang Med Univ, Int Joint Lab Recombinant Pharmaceut Prot Express, Xinxiang 453003, Peoples R China
基金
中国国家自然科学基金;
关键词
Chinese hamster ovary cells; protein of interest; clone aggregation; protein aggregation; culture process; MONOCLONAL-ANTIBODY; CHO-CELLS; GENE-EXPRESSION; THERAPEUTIC PROTEINS; MAMMALIAN-CELLS; INTERFERON-BETA; CULTURE-MEDIA; AGGREGATION; LINES; STRATEGIES;
D O I
10.3390/ijms26031324
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:14
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共 119 条
[91]   The use of site-specific recombination and cassette exchange technologies for monoclonal antibody production in Chinese Hamster ovary cells: retrospective analysis and future directions [J].
Srirangan, Kajan ;
Loignon, Martin ;
Durocher, Yves .
CRITICAL REVIEWS IN BIOTECHNOLOGY, 2020, 40 (06) :833-851
[92]   Utilizing a regulated targeted integration cell line development approach to systematically investigate what makes an antibody difficult to express [J].
Tadauchi, Tomofumi ;
Lam, Cynthia ;
Liu, Laura ;
Zhou, Yizhou ;
Tang, Danming ;
Louie, Salina ;
Snedecor, Brad ;
Misaghi, Shahram .
BIOTECHNOLOGY PROGRESS, 2019, 35 (02)
[93]  
Tihanyi Borbala, 2020, Drug Discov Today Technol, V38, P25, DOI 10.1016/j.ddtec.2021.02.003
[94]   The use of catechins in Chinese hamster ovary cell media for the improvement of monoclonal antibody yields and a reduction of acidic species [J].
Toronjo-Urquiza, Luis ;
Acosta-Martin, Adelina E. ;
James, David C. ;
Nagy, Tibor ;
Falconer, Robert J. .
BIOTECHNOLOGY PROGRESS, 2020, 36 (04)
[95]   The secretory pathway - the key for unlocking the potential of Chinese hamster ovary cell factories for manufacturing therapeutic proteins [J].
Torres, Mauro ;
Hussain, Hirra ;
Dickson, Alan J. .
CRITICAL REVIEWS IN BIOTECHNOLOGY, 2023, 43 (04) :628-645
[96]   Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development [J].
Tripathi, Nagesh K. ;
Shrivastava, Ambuj .
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY, 2019, 7
[97]   Heat Shock Proteins; An Overview [J].
Tutar, Lutfi ;
Tutar, Yusuf .
CURRENT PHARMACEUTICAL BIOTECHNOLOGY, 2010, 11 (02) :216-222
[98]   Aggregates in Monoclonal Antibody Manufacturing Processes [J].
Vazquez-Rey, Maria ;
Lang, Dietmar A. .
BIOTECHNOLOGY AND BIOENGINEERING, 2011, 108 (07) :1494-1508
[99]   Mechanisms underlying epigenetic and transcriptional heterogeneity in Chinese hamster ovary (CHO) cell lines [J].
Veith, Nathalie ;
Ziehr, Holger ;
MacLeod, Roderick A. F. ;
Reamon-Buettner, Stella Marie .
BMC BIOTECHNOLOGY, 2016, 16
[100]   Biopharmaceutical benchmarks 2022 [J].
Walsh, Gary ;
Walsh, Eithne .
NATURE BIOTECHNOLOGY, 2022, 40 (12) :1722-1760