An advanced bioreactor facility for automated, industry-aligned production of high-value proteins

先进的生物反应器设施，用于自动化、符合行业生产高价值蛋白质

• 批准号: BB/R013802/1
• 负责人: Colin Robinson
• 金额: $ 47.48万
• 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: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR013802%2F1
• 关键词: advanced; bioreactor; facility; automated; industry

The production of recombinant proteins is a critically important area in biology, and many proteins are currently produced in bacterial, yeast or mammalian cells and then purified so that their structures and mechanisms can be studied in detail. However, recombinant protein production is also a central part of the biotechnology industry, because many of the most powerful medicines are 'biopharmaceuticals' such as anti-cancer or anti-inflammatory antibodies, cytokines, growth hormones and others. The worldwide biopharmaceutical industry is valued at over $160 billion p.a. and it is growing rapidly. Research into new biopharmaceutical drugs and expression systems is a major priority in the UK.Many academic groups work closely with Biotechnology companies to develop new cell lines with enhanced properties, but whereas companies use sophisticated equipment to grow cells and produce proteins in large amounts, such systems are rarely available to academic groups. This means that there is a significant mismatch in efforts, and cell growth protocols developed by academics cannot be simply adopted by their industrial partners. Instead, new growth and protein expression protocols have to be developed from scratch. In this application we propose to purchase an ambr250 bioreactor system, which allows highly automated growth of bacterial or mammalian cells at very high density. The bioreactor volumes are only 100-250 ml but it has been shown that the results are highly scalable; in other words, growth protocols developed using this system almost invariably work when used used in much larger reactor vessels. The system will be installed in a purpose-designed unit and used in two broad types of project:(i). Groups working on biotechnology projects, where the aim is to produce high-value proteins such as biopharmaceuticals, will benefit from the equipment because they will be able to carry out research under industry-mimicking conditions. This will enhance progress in a number of important projects at Kent and elsewhere, and the equipment will also be used to enhance work in a new 'Global Challenges' research project involving Kent, Imperial College and University College London. This project aims to enable countries in South East Asia to produce their own biopharmaceuticals, most of which are simply too expensive for the vast majority (over 90%) of patients. (ii). Groups working on more fundamental areas of science, where large quantities of recombinant protein are required, will benefit because the ambr250 system can produce cells at high densities and target proteins are often produced at concentration of over 1 gram per litre of culture - easily enough for most research projects.The proposed facility will be used by the applicants and also made available to external users. It will be unique among academic Institutions in the UK: UCL is the only University in possession of an ambr250 system and this is not available to external users. The primary reason for the low presence of this equipment in academia is the cost of the bioreactors, which are expensive and single-use. To circumvent this problem and ensure availability to the academic community, the University of Kent has committed a total of £80,000 for the sole purpose of providing bioreactors free of charge over the first four years of the facility's existence. This will provide a huge boost to uptake by external users and we predict that many groups will be able to capitalise on the system's exceptional performance.

重组蛋白的生产是生物学中一个至关重要的领域，目前许多蛋白质在细菌、酵母或哺乳动物细胞中生产，然后纯化，以便可以详细研究其结构和机制。然而，重组蛋白生产也是生物技术产业的核心部分，因为许多最强大的药物是“生物制药”，如抗癌或抗炎抗体，细胞因子，生长激素等。全球生物制药行业每年价值超过1600亿美元。而且还在快速增长在英国，对新的生物制药药物和表达系统的研究是一个主要的优先事项。许多学术团体与生物技术公司密切合作，开发具有增强特性的新细胞系，但尽管公司使用先进的设备来培养细胞和大量生产蛋白质，但学术团体很少使用这种系统。这意味着在努力方面存在显著的不匹配，学术界开发的细胞生长协议不能简单地被他们的工业合作伙伴采用。相反，新的生长和蛋白质表达方案必须从头开始开发。在本申请中，我们建议购买ambr 250生物反应器系统，该系统允许细菌或哺乳动物细胞以非常高的密度高度自动化生长。生物反应器的体积仅为100 - 250 ml，但已显示结果是高度可扩展的;换句话说，使用该系统开发的生长方案在用于大得多的反应器容器中时几乎总是有效。该系统将安装在一个专门设计的单元中，并用于两大类项目：从事生物技术项目的团体，其目的是生产高价值的蛋白质，如生物制药，将受益于该设备，因为他们将能够在模拟工业的条件下进行研究。这将促进肯特和其他地方的一些重要项目的进展，这些设备还将用于加强一个新的"全球挑战"研究项目的工作，该项目涉及肯特、帝国理工学院和伦敦大学学院。该项目旨在使东南亚国家能够生产自己的生物药品，其中大多数对绝大多数（超过90%）患者来说过于昂贵。（二）.在需要大量重组蛋白的基础科学领域工作的团体将受益，因为ambr 250系统可以以高密度生产细胞，并且目标蛋白的浓度通常超过每升培养物1克-对于大多数研究项目来说足够容易。拟议的设施将由申请人使用，也可供外部用户使用。它将是英国学术机构中独一无二的：UCL是唯一拥有ambr250系统的大学，这是不提供给外部用户的。这种设备在学术界存在率低的主要原因是生物反应器的成本，这些生物反应器昂贵且一次性使用。为了解决这个问题，并确保学术界的可用性，肯特大学已承诺在设施存在的前四年内免费提供生物反应器的唯一目的是80，000英镑。这将极大地推动外部用户的使用，我们预测许多团体将能够利用该系统的卓越性能。

项目成果

High throughput automated microbial bioreactor system used for clone selection and rapid scale-down process optimization.

• DOI: 10.1002/btpr.2534
• 发表时间: 2018-01
• 期刊: Biotechnology progress
• 影响因子: 2.9
• 作者: Velez-Suberbie ML;Betts JPJ;Walker KL;Robinson C;Zoro B;Keshavarz-Moore E
• 通讯作者: Keshavarz-Moore E

Novel constructs and 1-step chromatography protocols for the production of Porcine Circovirus 2d (PCV2d) and Circovirus 3 (PCV3) subunit vaccine candidates

• DOI: 10.1016/j.fbp.2021.10.001
• 发表时间: 2021-11-25
• 期刊: FOOD AND BIOPRODUCTS PROCESSING
• 影响因子: 4.6
• 作者: Peswani, Amber R.;Narkpuk, Jaraspim;Robinson, Colin
• 通讯作者: Robinson, Colin