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使用位点特异性重定向跳入平台细胞系来支持生物药物发现。

Use of the site-specific retargeting jump-in platform cell line to support biologic drug discovery.

作者信息

Butler Robin, Hornigold David, Huang Ling, Huntington Catherine, London Tim, Dillon Janette, Tigue Natalie J, Rossi Alessandra, Naylor Jacqueline, Wilkinson Trevor

机构信息

MedImmune, Antibody Discovery and Protein Engineering, Cambridge, UK

MedImmune, Cardiovascular and Metabolic Disease, Cambridge, UK.

出版信息

J Biomol Screen. 2015 Apr;20(4):528-35. doi: 10.1177/1087057114562715. Epub 2014 Dec 22.

Abstract

Biologics represent a fast-growing class of therapeutics in the pharmaceutical sector. Discovery of therapeutic antibodies and characterization of peptides can necessitate high expression of the target gene requiring the generation of clonal stably transfected cell lines. Traditional challenges of stable cell line transfection include gene silencing and cell-to-cell variability. Our inability to control these can present challenges in lead isolation. Recent progress in site-specific targeting of transgene to specific genomic loci has transformed the ability to generate stably transfected mammalian cell lines. In this article, we describe how the use of the Jump-In platform (Life Technologies, Carlsbad, CA) has been applied to drug discovery projects. It can easily and rapidly generate homogeneous high-expressing cell pools with a high degree of reproducibility. Their use in cell-based screening to identify specific binders, identify binding to relevant species variants, or detect functionally relevant therapeutic antibodies is central in driving drug discovery.

摘要

生物制剂是制药领域中一类快速发展的治疗药物。治疗性抗体的发现和肽的表征可能需要靶基因的高表达,这就需要生成克隆稳定转染细胞系。稳定细胞系转染的传统挑战包括基因沉默和细胞间变异性。我们无法控制这些因素可能会在先导物分离中带来挑战。转基因在特定基因组位点的位点特异性靶向方面的最新进展改变了生成稳定转染哺乳动物细胞系的能力。在本文中,我们描述了Jump-In平台(赛默飞世尔科技公司,加利福尼亚州卡尔斯巴德)是如何应用于药物发现项目的。它可以轻松快速地生成具有高度可重复性的均匀高表达细胞池。它们在基于细胞的筛选中用于识别特异性结合物、识别与相关物种变体的结合或检测功能相关的治疗性抗体,这对于推动药物发现至关重要。

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