Translation of Step-changing Bioprocesses and Expression System Technologies for Next Generation Protein Biologics Production in CHO Cells

转化用于 CHO 细胞中下一代蛋白质生物制品生产的逐步改变的生物过程和表达系统技术

• 批准号: BB/N023501/1
• 负责人: Christopher Smales
• 金额: $ 95.09万
• 依托单位: University of Kent
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FN023501%2F1
• 关键词: Translation; Step; changing; Bioprocesses; Expression

Chinese hamster ovary (CHO) cells are the main production host for >US$145billion/yr of protein biologics used as medicines for a range of diseases. The CHO platform is mature when considering production of monoclonal antibodies, but new format non-native molecules such as fusion proteins, antibody fragments and other exotic molecules remain difficult to express (DTE) in this, or any other host. This project builds upon proof of concept work demonstrating that engineering the CHO chassis, together with growth media manipulation, increases both the yield and quality of a number of DTE proteins that are in development for application to unmet clinical needs and diseases with no current treatments. The project will advance the technology readiness level of our preliminary findings beyond proof-of-concept to deliver the commercialization of new CHO cell systems for DTE proteins and associated bioprocesses ready for industrial application to produce these important new medicines.

中国仓鼠卵巢（CHO）细胞是每年超过1450亿美元的蛋白质生物制剂的主要生产宿主，这些蛋白质生物制剂用作一系列疾病的药物。当考虑生产单克隆抗体时，CHO平台是成熟的，但是新形式的非天然分子如融合蛋白、抗体片段和其他外来分子仍然难以在该宿主或任何其他宿主中表达（DTE）。该项目建立在概念验证工作的基础上，证明了工程化CHO底盘，以及生长培养基操作，提高了许多DTE蛋白的产量和质量，这些蛋白正在开发中，用于未满足的临床需求和目前没有治疗方法的疾病。该项目将推进我们初步发现的技术准备水平，超越概念验证，以实现DTE蛋白质和相关生物过程的新CHO细胞系统的商业化，为工业应用生产这些重要的新药做好准备。

项目成果

Manipulation of mRNA translation elongation influences the fragmentation of a biotherapeutic Fc-fusion protein produced in CHO cells.

• DOI: 10.1002/bit.28230
• 发表时间: 2022-12
• 期刊: BIOTECHNOLOGY AND BIOENGINEERING
• 影响因子: 3.8
• 作者: Knight, Tanya J.;Povey, Jane F.;Vito, Davide;Mohindra, Atul;Jaques, Colin M.;Smales, C. Mark
• 通讯作者: Smales, C. Mark

A proline metabolism selection system and its application to the engineering of lipid biosynthesis in Chinese hamster ovary cells.

• DOI: 10.1016/j.mec.2021.e00179
• 发表时间: 2021-12
• 期刊: Metabolic engineering communications
• 影响因子: 5.2
• 作者: Budge JD;Roobol J;Singh G;Mozzanino T;Knight TJ;Povey J;Dean A;Turner SJ;Jaques CM;Young RJ;Racher AJ;Smales CM
• 通讯作者: Smales CM

Engineering of Chinese Hamster Ovary Cells With NDPK-A to Enhance DNA Nuclear Delivery Combined With EBNA1 Plasmid Maintenance Gives Improved Exogenous Transient Reporter, mAb and SARS-CoV-2 Spike Protein Expression.

• DOI: 10.3389/fbioe.2021.679448
• 发表时间: 2021
• 期刊: Frontiers in bioengineering and biotechnology
• 影响因子: 5.7
• 作者: Budge JD;Young RJ;Smales CM
• 通讯作者: Smales CM

Meta-Analysis of Publicly Available Chinese Hamster Ovary (CHO) Cell Transcriptomic Datasets for Identifying Engineering Targets to Enhance Recombinant Protein Yields.

对公开的中国仓鼠卵巢 (CHO) 细胞转录组数据集进行荟萃分析，以确定提高重组蛋白产量的工程目标。

• DOI: 10.1002/biot.201800066
• 发表时间: 2018
• 期刊: Biotechnology journal
• 影响因子: 4.7
• 作者: Tamošaitis L

Effects of lysosomal biotherapeutic recombinant protein expression on cell stress and protease and general host cell protein release in Chinese hamster ovary cells.

• DOI: 10.1002/btpr.2455
• 发表时间: 2017-05
• 期刊: Biotechnology progress
• 影响因子: 2.9
• 作者: Migani D;Smales CM;Bracewell DG
• 通讯作者: Bracewell DG