Genome engineering and synthetic biology approaches for improving industrial CHO cell production of biologics

用于改善工业 CHO 细胞生物制剂生产的基因组工程和合成生物学方法

• 批准号: BB/M028933/1
• 负责人: Mark Isalan
• 金额: $ 12.55万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM028933%2F1
• 关键词: Genome; engineering; synthetic; biology; approaches

Biologics are protein-based biopharmaceutical drugs that are used in a variety of diseases. The overall market for biopharmaceuticals is steadily increasing and in 2013 generated sales in excess of $140 billion. The Lonza GS platform is considered industry leading with 18 marketed products, and over 100 in active human trials. Despite this success, there are increasing numbers of "difficult-to-express" biologics reaching the pipeline. The new technologies of rational genome and gene circuit engineering promise new ways of regulating biologic expression to maximise production, while reducing toxicity. The aim is to build "genetic thermostats" to prevent toxic proteins from shutting down cellular production altogether, using genetic feedback. The final goal of this feasibility study is to pave the way for the development of a robust and one-fits-all cell line platform for the production of "difficult-to-express" biologics.

生物制剂是基于蛋白质的生物制药药物，用于各种疾病。生物制药的整体市场正在稳步增长，2013年的销售额超过1400亿美元。Lonza GS平台被认为是行业领先的，有18种上市产品，100多种正在进行人体试验。尽管取得了这一成功，但越来越多的“难以表达”的生物制剂进入了管道。合理基因组和基因电路工程的新技术为调节生物表达提供了新的方法，以最大限度地提高产量，同时降低毒性。其目的是建立“遗传恒温器”，以防止有毒蛋白质完全关闭细胞生产，利用遗传反馈。这项可行性研究的最终目标是为开发一个强大的、一刀切的细胞系平台铺平道路，用于生产“难以表达”的生物制剂。