Application of Process Raman Spectroscopy for bioprocessing using gene edited production hosts and cell-free systems

过程拉曼光谱在使用基因编辑生产宿主和无细胞系统的生物加工中的应用

• 批准号: 2827524
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2827524
• 关键词: Application; Process; Raman; Spectroscopy; bioprocessing

Raman spectroscopy (RS) is a non-destructive vibrational spectroscopy technique that provides sharp spectral features that correlate to a sample's chemical or molecular structure in aqueous solution. Raman measurements of biological molecules, cells and tissues have been well established with many biomedical applications focused on disease detection and in vivo glucose monitoring. In parallel there has been substantial developments in the use of RS to monitor fermentation processes. In situ, simultaneous measurement of nutrients, metabolites or by-products, cell density (or biomass), have made RS an important Process Analytical Technology in industrial bioprocessing. A number of global biomanufacturers including for example Lonza, GSK, Merck Novartis Hoffman La Roche have already implemented online Raman Spectroscopy for process control and optimisation of biomanufacturing. Whilst genome editing has opened up opportunities in gene and cell therapy applications, it can also be used in bioprocessing to improve cell growth characteristics; cell productivity and product titre and optimise and/or improve product quality; improve cell free extracts as production hosts. An alternative to cell culture for bioprocessing is the use of cell-free protein expression (CPE) systems based on cell lysates. Recently CPE has been demonstrated as a potential production host for a variety of biologics, vaccines and antimicrobials. The advantages of CPE systems for bioprocessing it that they are non-living and not prone to contamination, have semi-defined components and an assay format that offer flexibility in adjusting the reaction mix and expression process. The overall aim of the proposed project is to explore the application of RS into new areas such as genome edited cell cultures and cell-free systems with an industrial collaborator Kaiser (Endres-Hauser group) who design and manufacture Raman probes. The proposed project brings together the expertise of Freemont group in CPE and cell culture, the Kazarian group in RS and London Biofoundry in synthetic biology tool development.

拉曼光谱（RS）是一种非破坏性振动光谱技术，可提供与水溶液中样品的化学或分子结构相关的清晰光谱特征。生物分子、细胞和组织的拉曼测量已经在许多生物医学应用中得到了很好的应用，重点是疾病检测和体内血糖监测。与此同时，在利用RS监测发酵过程方面也有了实质性的发展。原位同时测量营养物质、代谢物或副产品、细胞密度（或生物量），使RS成为工业生物加工中重要的过程分析技术。包括龙沙、葛兰素史克、默克诺华、霍夫曼罗氏在内的许多全球生物制药商已经实施了在线拉曼光谱技术，用于生物制造的过程控制和优化。虽然基因组编辑为基因和细胞治疗应用开辟了机会，但它也可以用于生物加工，以改善细胞生长特性；生产效率和产品质量，优化和/或提高产品质量；改善无细胞提取物作为生产宿主。生物处理细胞培养的替代方法是使用基于细胞裂解物的无细胞蛋白表达（CPE）系统。最近，CPE已被证明是多种生物制剂、疫苗和抗菌剂的潜在生产宿主。用于生物处理的CPE系统的优点是它们是非生物的，不易受到污染，具有半定义的成分和可灵活调整反应混合和表达过程的分析格式。拟议项目的总体目标是探索RS在基因组编辑细胞培养和无细胞系统等新领域的应用，与设计和制造拉曼探针的工业合作伙伴Kaiser （Endres-Hauser集团）合作。拟议的项目汇集了Freemont集团在CPE和细胞培养方面的专业知识，Kazarian集团在RS和London bifoundry在合成生物学工具开发方面的专业知识。