A Platform for the CHO Biomanufacturing Systems Biology Community

CHO 生物制造系统生物学界的平台

• 批准号: 1412365
• 负责人: Kelvin Lee
• 金额: $ 80万
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1412365&HistoricalAwards=false
• 关键词: Platform; CHO; Biomanufacturing; Systems; Biology

The award, funded by the Systems and Synthetic Biology Program in MCB and the Biotechnology, Biochemical and Biomass Engineering Program in CBET will provide tools and infrastructure needed to help in the biomanufacturing of protein-based high value products that can be used in a variety of applications, including as medicines. A majority of these proteins are manufactured using "mammalian cells" and represents more than $60,000,000,000 per year in sales. There are numerous problems and issues in the biomanufacturing of these proteins that have not been adequately addressed because of incomplete knowledge of how the most common cell platform technology (known as the Chinese hamster ovary or CHO cell) functions. Recently, the genome of the CHO cell has been published and shared and an international community of academic and industrial partners has emerged to organize and build upon this new knowledge. The work that will be pursued during this project will provide necessary tools and infrastructure to support the CHO genome effort, lead to a better understanding of some of the causes for problems in the biomanufacturing of proteins, and has the potential to substantially reduce the manufacturing cost of some of the most expensive biologics. Besides its importance for the research and manufacturing in the biotechnology industry, the project will also involve training of the workforce for this rapidly expanding sector of the US economy.Technical description: The establishment of the CHO K1 (a cell line) genome, together with two different versions of the Chinese hamster, offers the possibility of establishing a new reference genome and a number of related resources for this community. In Aim 1, the project will test different approaches to merge the two existing Chinese hamster genomes using a variety of bioinformatic approaches. This effort will create a new reference genome that benefits from the chromosomal information contained in one of the genomes with the high coverage depth in the other of the Chinese hamster genomes. In Aim 2, the project will develop and share bioinformatic tools related to mRNA and peptide/protein expression that should provide enhanced functionality to the current CHO genome browser. Aim 2 will also provide a resource for establishing product quality limits by offering a framework for calculating the range of possible glycoforms available to any given CHO cell. In Aim 3, the project will, for the first time, establish a framework to define genome and chromosomal (in)stability which forms the basis for important problems in biomanufacturing.

该奖项由MCB的系统和合成生物学计划以及CBET的生物技术，生化和生物量工程计划提供的奖项将提供所需的工具和基础设施，以帮助可以在包括药物在内的各种应用中使用的基于蛋白质的高价值产品生物制造，这些产品可用于蛋白质基于蛋白质的高价值产品。这些蛋白质中的大多数是使用“哺乳动物细胞”制造的，代表每年销售额超过60,000,000,000美元。这些蛋白质的生物制造中存在许多问题和问题，这些蛋白质尚未得到充分解决，因为对最常见的细胞平台技术（称为中国仓鼠卵巢或CHO细胞）的功能不完全了解。最近，Cho细胞的基因组已发表并共享，并且出现了一个学术和工业伙伴的国际社会，以组织和建立这些新知识。该项目期间将要进行的工作将提供必要的工具和基础设施来支持CHO基因组努力，从而更好地了解蛋白质生物制造中问题的某些原因，并有可能大大降低一些最昂贵的生物学的制造成本。除了它对生物技术行业的研究和制造业的重要性外，该项目还将涉及为美国经济的快速扩展领域的劳动力培训。技术描述：建立CHO K1（一个细胞系）基因组，以及中国仓鼠的两个不同版本的基因组，提供了一个新的参考基因资源和一个相关资源的可能性。在AIM 1中，该项目将使用各种生物信息学方法测试不同的方法，以合并两个现有的中国仓鼠基因组。这项工作将创建一个新的参考基因组，该基因组受益于一种基因组中的染色体信息，其中一个中国仓鼠基因组的覆盖深度很高。在AIM 2中，该项目将开发和共享与mRNA和肽/蛋白质表达相关的生物信息学工具，这些工具应为当前的CHO基因组浏览器提供增强的功能。 AIM 2还将通过提供一个框架来计算任何给定的CHO细胞可用的糖型范围，以提供建立产品质量限制的资源。在AIM 3中，该项目将首次建立一个框架来定义基因组和染色体（IN）稳定性，这构成了生物制造中重要问题的基础。