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

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2025年 / 26卷 / 03期

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.

引用

页数：14

共 119 条

[1] An Integrated Approach to Aggregate Control for Therapeutic Bispecific Antibodies Using an Improved Three Column Mab Platform-Like Purification Process [J].

Andrade, Cassia ;

Arnold, Lindsay ;

Motabar, Dana ;

Aspelund, Matthew ;

Tang, Alison ;

Hunter, Alan ;

Chung, Wai Keen .

BIOTECHNOLOGY PROGRESS, 2019, 35 (01)

[2] Determination of Chinese hamster ovary cell line stability and recombinant antibody expression during long-term culture [J].

Bailey, Laura A. ;

Hatton, Diane ;

Field, Ray ;

Dickson, Alan J. .

BIOTECHNOLOGY AND BIOENGINEERING, 2012, 109 (08) :2093-2103

[3] CHOPPI: A Web Tool for the Analysis of Immunogenicity Risk from Host Cell Proteins in CHO-Based Protein Production [J].

Bailey-Kellogg, Chris ;

Gutierrez, Andres H. ;

Moise, Leonard ;

Terry, Frances ;

Martin, William D. ;

De Groot, Anne S. .

BIOTECHNOLOGY AND BIOENGINEERING, 2014, 111 (11) :2170-2182

[4] Recurring genomic structural variation leads to clonal instability and loss of productivity [J].

Bandyopadhyay, Arpan A. ;

O'Brien, Sofie A. ;

Zhao, Liang ;

Fu, Hsu-Yuan ;

Vishwanathan, Nandita ;

Hu, Wei-Shou .

BIOTECHNOLOGY AND BIOENGINEERING, 2019, 116 (01) :41-53

[5] Stability of protein production from recombinant mammalian cells [J].

Barnes, LM ;

Bentley, CM ;

Dickson, AJ .

BIOTECHNOLOGY AND BIOENGINEERING, 2003, 81 (06) :631-639

[6] Autophagy and intracellular product degradation genes identified by systems biology analysis reduce aggregation of bispecific antibody in CHO cells [J].

Barzadd, Mona Moradi ;

Lundqvist, Magnus ;

Harris, Claire ;

Malm, Magdalena ;

Volk, Anna-Luisa ;

Thalen, Niklas ;

Chotteau, Veronique ;

Grassi, Luigi ;

Smith, Andrew ;

Abadi, Marina Leal ;

Lambiase, Giulia ;

Gibson, Suzanne ;

Hatton, Diane ;

Rockberg, Johan .

NEW BIOTECHNOLOGY, 2022, 68 :68-76

[7] Evaluation of different vector design strategies for the expression of recombinant monoclonal antibody in CHO cells [J].

Bayat, Hadi ;

Hossienzadeh, Saghar ;

Pourmaleki, Eshagh ;

Ahani, Roshanak ;

Rahimpour, Azam .

PREPARATIVE BIOCHEMISTRY & BIOTECHNOLOGY, 2018, 48 (02) :160-164

[8] Transposase-CRISPR mediated targeted integration (TransCRISTI) in the human genome [J].

Bazaz, Mahere Rezazade ;

Seno, Mohammad M. Ghahramani ;

Dehghani, Hesam .

SCIENTIFIC REPORTS, 2022, 12 (01)

[9] Reversible NaCl-induced aggregation of a monoclonal antibody at low pH: Characterization of aggregates and factors affecting aggregation [J].

Bickel, Fabian ;

Herold, Eva Maria ;

Signes, Alba ;

Romeijn, Stefan ;

Jiskoot, Wim ;

Kiefer, Hans .

EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2016, 107 :310-320

[10] PiggyBac transposase and transposon derivatives for gene transfer targeting the ribosomal DNA loci of CHO cells [J].

Bire, Solenne ;

Dusserre, Yves ;

Bigot, Yves ;

Mermod, Nicolas .

JOURNAL OF BIOTECHNOLOGY, 2021, 341 :103-112

← 1 2 3 4 5 6 7 8 9 10 →