重组蛋白生产CHO细胞系的研究进展

Q1 Pharmacology, Toxicology and Pharmaceutics Drug Discovery Today: Technologies Pub Date : 2020-12-01 DOI:10.1016/j.ddtec.2021.02.003
Borbála Tihanyi, László Nyitray
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引用次数: 67

摘要

用于生物医学研究、诊断和不同治疗的重组蛋白大多是在制药行业的中国仓鼠卵巢细胞中生产的。这些生物治疗药物,特别是单克隆抗体,在过去的几十年里已经显示出显著的市场增长。对大量生物制剂的需求不断增加,需要不断优化和改进生产技术。研究的目的是发现更好的手段和方法,达到更高的容量,同时保持稳定的产品质量。越来越多的复杂的新型蛋白质疗法,如病毒抗原、疫苗、双特异性和三特异性单克隆抗体,目前正在进入工业生产管道。在许多情况下,这些生物分子难以表达,需要定制产品特定的解决方案来改善其瞬时或稳定的生产。这些需求推动了更高效的表达优化系统和高通量筛选平台的发展,以促进产品特异性细胞系工程和生产策略的设计。在这篇综述中,我们概述了CHO细胞系发育、靶向基因组操作技术、选择系统和筛选方法的最新进展,目前用于重组蛋白的生产。
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Recent advances in CHO cell line development for recombinant protein production

Recombinant proteins used in biomedical research, diagnostics and different therapies are mostly produced in Chinese hamster ovary cells in the pharmaceutical industry. These biotherapeutics, monoclonal antibodies in particular, have shown remarkable market growth in the past few decades. The increasing demand for high amounts of biologics requires continuous optimization and improvement of production technologies. Research aims at discovering better means and methods for reaching higher volumetric capacity, while maintaining stable product quality. An increasing number of complex novel protein therapeutics, such as viral antigens, vaccines, bi- and tri-specific monoclonal antibodies, are currently entering industrial production pipelines. These biomolecules are, in many cases, difficult to express and require tailored product-specific solutions to improve their transient or stable production. All these requirements boost the development of more efficient expression optimization systems and high-throughput screening platforms to facilitate the design of product-specific cell line engineering and production strategies. In this minireview, we provide an overview on recent advances in CHO cell line development, targeted genome manipulation techniques, selection systems and screening methods currently used in recombinant protein production.

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来源期刊
Drug Discovery Today: Technologies
Drug Discovery Today: Technologies Pharmacology, Toxicology and Pharmaceutics-Drug Discovery
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期刊介绍: Discovery Today: Technologies compares different technological tools and techniques used from the discovery of new drug targets through to the launch of new medicines.
期刊最新文献
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