Effect of Apoptosis and Autophagy on Recombinant Protein Expression in Chinese Hamster Ovary Cells

IF 3.1 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS
Hui-Jie Zhang, Qi Zhao, Jumai Abiti, Yan-Ping Gao, Ming-Ming Han, Hai-Tong Wang, Xi Zhang, Jia-Ning Wang, Jia-Liang Guo, Xiao-Yin Wang, Zi-Chun Hua, Tian-Yun Wang, Yan-Long Jia
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Abstract

Chinese hamster ovary (CHO) cells serve as a cornerstone platform for producing diverse therapeutic recombinant proteins, including monoclonal antibodies, vaccines, and hormones. Apoptosis and autophagy emerge as critical biological factors that directly impair cell proliferation and limit recombinant protein production. These cellular processes diminish CHO cell viability and reduce culture density, ultimately compromising protein yield and product quality. While apoptosis and autophagy exhibit distinct molecular mechanisms, they demonstrate functional interdependence in cellular regulation. This interrelationship highlights the importance of coordinated pathway modulation as an effective approach to improve both cell growth performance and recombinant protein synthesis. This review examines the complex interplay between apoptosis and autophagy pathways, their collective impact on recombinant protein expression, and contemporary strategies for developing stable anti-apoptotic/anti-autophagy cell lines. Through systematic analysis of these critical elements, we present optimized engineering approaches to enhance CHO cell culture systems and biopharmaceutical manufacturing processes, with the goal of facilitating more efficient therapeutic protein production.

SUMMARY

  • Crosstalk mechanisms between apoptosis and autophagy in CHO cell cultures.

  • Recent advances in real-time monitoring of apoptosis and autophagy.

  • Strategic mitigation of apoptosis/autophagy to improve recombinant protein yields.

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凋亡和自噬对中国仓鼠卵巢细胞重组蛋白表达的影响
中国仓鼠卵巢(CHO)细胞是生产多种治疗性重组蛋白的基础平台,包括单克隆抗体、疫苗和激素。凋亡和自噬是直接影响细胞增殖和限制重组蛋白产生的关键生物学因素。这些细胞过程降低CHO细胞活力,降低培养密度,最终影响蛋白质产量和产品质量。虽然细胞凋亡和自噬表现出不同的分子机制,但它们在细胞调节中表现出功能上的相互依赖性。这种相互关系突出了协调通路调节作为提高细胞生长性能和重组蛋白合成的有效途径的重要性。本文综述了细胞凋亡和自噬途径之间复杂的相互作用,它们对重组蛋白表达的共同影响,以及发展稳定的抗凋亡/抗自噬细胞系的当代策略。通过对这些关键因素的系统分析,我们提出了优化的工程方法来增强CHO细胞培养系统和生物制药制造工艺,目的是促进更有效的治疗性蛋白质生产。CHO细胞培养中凋亡和自噬之间的串扰机制。细胞凋亡和自噬实时监测的最新进展。策略性减缓细胞凋亡/自噬以提高重组蛋白产量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Biotechnology Journal
Biotechnology Journal Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
8.90
自引率
2.10%
发文量
123
审稿时长
1.5 months
期刊介绍: Biotechnology Journal (2019 Journal Citation Reports: 3.543) is fully comprehensive in its scope and publishes strictly peer-reviewed papers covering novel aspects and methods in all areas of biotechnology. Some issues are devoted to a special topic, providing the latest information on the most crucial areas of research and technological advances. In addition to these special issues, the journal welcomes unsolicited submissions for primary research articles, such as Research Articles, Rapid Communications and Biotech Methods. BTJ also welcomes proposals of Review Articles - please send in a brief outline of the article and the senior author''s CV to the editorial office. BTJ promotes a special emphasis on: Systems Biotechnology Synthetic Biology and Metabolic Engineering Nanobiotechnology and Biomaterials Tissue engineering, Regenerative Medicine and Stem cells Gene Editing, Gene therapy and Immunotherapy Omics technologies Industrial Biotechnology, Biopharmaceuticals and Biocatalysis Bioprocess engineering and Downstream processing Plant Biotechnology Biosafety, Biotech Ethics, Science Communication Methods and Advances.
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