MAT2A Knockdown Enhances Recombinant Protein Expression in Transgenic CHO Cells Through Regulation of Cell Cycle.

IF 3.5 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology and Bioengineering Pub Date : 2025-02-26 DOI:10.1002/bit.28962

Yan-Ping Gao, Jiang-Tao Lu, Hui-Jie Zhang, Zhao-Ming Cui, Yang Guo, Xi Zhang, Wen Wang, Le-Le Qiu, Xiao-Yin Wang, Tian-Yun Wang, Yan-Long Jia

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引用次数: 0

Abstract

Chinese hamster ovary (CHO) cells represent the most widely utilized host system for industrial production of high-quality recombinant protein therapeutics. Novel CHO cell line development is achieved through genetic and cellular engineering approaches, effectively addressing limitations such as clonal variation and productivity loss during culture. Previous studies have established that MAT2A inhibition in tumor cells promotes expression of the cyclin-dependent kinase inhibitor p21, inducing antitumor activity. Notably, p21 induction has been shown to enhance recombinant protein expression in CHO cells by triggering cell cycle arrest. In this study, we identified MAT2A as a potential regulatory target, showing significant differential expression in transfected CHO cells with elevated versus diminished recombinant protein production. To investigate this phenomenon, we generated CHO cells with MAT2A knockdown (shMAT2A) and evaluated their recombinant protein output. Results demonstrated that MAT2A silencing enhanced recombiant protein/antibody production by 1.73-/1.70-fold through suppression of CyclinD1, thereby activating p21 and inducing G1 phase arrest. Furthermore, pharmacological inhibition of MAT2A using small molecules increased cell volume, boosted metabolic activity, and improved specific antibody productivity of recombiant protein/antibody production by 1.88-/2.16-fold in transfected CHO cells. These findings advance our understanding of MAT2A-mediated regulatory mechanisms and provide a strategic framework for developing high-efficiency CHO cell expression systems.

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来源期刊

Biotechnology and Bioengineering 工程技术-生物工程与应用微生物

CiteScore

7.90

自引率

5.30%

发文量

280

审稿时长

2.1 months

期刊介绍： Biotechnology & Bioengineering publishes Perspectives, Articles, Reviews, Mini-Reviews, and Communications to the Editor that embrace all aspects of biotechnology. These include: -Enzyme systems and their applications, including enzyme reactors, purification, and applied aspects of protein engineering -Animal-cell biotechnology, including media development -Applied aspects of cellular physiology, metabolism, and energetics -Biocatalysis and applied enzymology, including enzyme reactors, protein engineering, and nanobiotechnology -Biothermodynamics -Biofuels, including biomass and renewable resource engineering -Biomaterials, including delivery systems and materials for tissue engineering -Bioprocess engineering, including kinetics and modeling of biological systems, transport phenomena in bioreactors, bioreactor design, monitoring, and control -Biosensors and instrumentation -Computational and systems biology, including bioinformatics and genomic/proteomic studies -Environmental biotechnology, including biofilms, algal systems, and bioremediation -Metabolic and cellular engineering -Plant-cell biotechnology -Spectroscopic and other analytical techniques for biotechnological applications -Synthetic biology -Tissue engineering, stem-cell bioengineering, regenerative medicine, gene therapy and delivery systems The editors will consider papers for publication based on novelty, their immediate or future impact on biotechnological processes, and their contribution to the advancement of biochemical engineering science. Submission of papers dealing with routine aspects of bioprocessing, description of established equipment, and routine applications of established methodologies (e.g., control strategies, modeling, experimental methods) is discouraged. Theoretical papers will be judged based on the novelty of the approach and their potential impact, or on their novel capability to predict and elucidate experimental observations.