药学学报, 2020, 55(12): 2989-2993
引用本文:
崔颖, 白玉, 程速远. 重组蛋白药物生产用哺乳动物细胞系构建中筛选标记的应用现状及审评思考[J]. 药学学报, 2020, 55(12): 2989-2993.
CUI Ying, BAI Yu, CHENG Su-yuan. Considerations and application status of selection marker for generation of recombinant biologics producing mammalian cell lines[J]. Acta Pharmaceutica Sinica, 2020, 55(12): 2989-2993.

重组蛋白药物生产用哺乳动物细胞系构建中筛选标记的应用现状及审评思考
崔颖, 白玉, 程速远
国家药品监督管理局药品审评中心, 北京 100022
摘要:
对于重组蛋白药物开发,短时间内构建筛选高表达稳定的单克隆细胞株是工业界最主要的挑战。筛选标记是质粒载体中的关键元件,在生产细胞系的构建和筛选中发挥重要作用,通过设计筛选标记提高筛选严谨性,以获得稳定高产细胞株,是一种改进细胞株开发工艺的有效手段。本文以中华仓鼠卵巢(Chinese hamaster overy,CHO)细胞为例,介绍筛选标记在重组蛋白药物生产用哺乳动物细胞系构建中的应用,设计筛选标记以提高筛选严谨性的方法,以及细胞基质稳定性及筛选标记安全性的审评思考,以期为药物研发机构高效开发重组蛋白药物提供参考。
关键词:    重组蛋白药物      中华仓鼠卵巢细胞      筛选标记      筛选严谨性      细胞基质稳定性      筛选标记安全性     
Considerations and application status of selection marker for generation of recombinant biologics producing mammalian cell lines
CUI Ying, BAI Yu, CHENG Su-yuan
Center for Drug Evaluation, National Medical Products Administration, Beijing 100022, China
Abstract:
The major challenge in the development of recombinant biologics lies in generating and isolating rare high-producing stable single clone in a short period of time. The selection marker is an essential component of the plasmid vector, it plays an important part in the generation and screening of producing cell lines. Engineering the selection marker to enhance the stringency of selection for high producing cells is one of the most effective approaches to improve the cell line development process. Here, using Chinese hamaster overy (CHO) cells as an example, we introduce the application of selection marker for generation of recombinant biologics producing mammalian cell lines, methods of engineering the selection markers to enhance the selection stringency, and propose considerations on cell substrate stability and selection marker safety, in order to provide references for high-efficiency development of recombinant biologics.
Key words:    recombinant biologics    CHO cell    selection marker    selection stringency    cell substrate stability    selection marker safety   
收稿日期: 2020-03-31
DOI: 10.16438/j.0513-4870.2020-0454
通讯作者: 程速远,Tel:86-10-68583020,E-mail:chengsy@cde.org.cn
Email: chengsy@cde.org.cn
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