Phase I I/UCRC University of Massachusetts Lowell Site: Advanced Mammalian Biomanufacturing Innovation Center (AMBIC)

I 期 I/UCRC 马萨诸塞大学洛厄尔分校地点：先进哺乳动物生物制造创新中心 (AMBIC)

• 批准号: 1624718
• 负责人: Seongkyu Yoon
• 金额: $ 75万
• 依托单位: University of Massachusetts Lowell
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1624718&HistoricalAwards=false
• 关键词: Phase; UCRC; University; Massachusetts; Lowell

Phase I I/UCRC University of Massachusetts Lowell Site: Advanced Mammalian Biomanufacturing Innovation Center (AMBIC).Johns Hopkins University, University of Delaware, Clemson University, and University of Massachusetts Lowell have jointly established a multi-university, Phase I I/UCRC entitled the Advanced Mammalian Biomanufacturing Innovation Center (AMBIC). Over the past two decades, the biopharmaceutical industry has emerged as one of the major manufacturing industries and engines of growth in the US economy. Biomanufacturing represents nearly 2% of the total US GDP and its fraction is expanding. Much of biomanufacturing involves the use of cells to make medicines. Examples of these types of medicines include cancer medicines and vaccines. A key element in developing these medicines is the need to establish complex manufacturing processes. AMBIC will implement engineering innovations to enhance the capabilities of our nation to manufacture these important life-extending and life-saving medicines. Such improvements will improve the competitiveness of US biomanufacturing in coming decades leading to more economic investment by these companies and more jobs for American workers. The mission of AMBIC is to develop enabling technologies, knowledge, design tools and methods that apply and integrate high-throughput and genome-based technologies to fast-track advanced biomanufacturing processes. AMBIC is the first I/UCRC dedicated to mammalian cell culture upstream development focusing on Chinese hamster ovary (CHO) cells, the principal biopharmaceutical production host of industry. AMBIC will bring together leading academic and industrial biotechnologists focused on mammalian cell culture manufacturing at a pre-competitive research level to address the complex problems in biopharmaceutical manufacturing. This multi-university center will allow AMBIC to leverage the skills and the expertise of many faculty members across the Sites. AMBIC will be a critical catalyst towards maintaining national excellence in biopharmaceutical production by conducting research in: 1) Understanding Industrially-Relevant Biology (e.g., all -omics, bioinformatics, process and product quality, etc.); 2) Process Monitoring & Control (e.g., analytics, instrumentation, data mining and modeling); 3) Consensus and Standardization Issues (e.g., standards, simple fingerprints, raw material issues, regulatory issues, forensic bioprocessing, clonality). Through systems-level biology analysis, novel cell line development, bioreactor optimization, and advanced analytics, AMBIC will provide transformative solutions that can lower biomanufacturing costs and improve bioprocessing efficiency. Most importantly, these advances may ultimately serve to make more biopharmaceuticals available to patients that need them and lower overall health care costs for consumers. In addition, AMBIC will establish and maintain a pipeline of educated and motivated students at multiple levels for careers in biopharmaceutical manufacturing and development. Collaborations with corporate partners will enable the students to work on the most pressing problems that the industry faces. Furthermore, this center will serve to engage and excite students from under-represented minority populations to pursue a career in life sciences, engineering, or related STEM fields. An important part of the AMBIC activities and a committed goal of the PI's is to increase the participation of women and under-represented minorities in STEM disciplines by energizing students from all backgrounds about the exciting opportunities to help others through STEM careers in biotechnology and biomedicine.

约翰霍普金斯大学、特拉华大学、克莱姆森大学和马萨诸塞大学洛厄尔分校联合成立了一个多所大学，第一阶段I/UCRC题为高级哺乳动物生物制造创新中心(AMBIC)。在过去的20年里，生物制药行业已经成为美国经济的主要制造业和增长引擎之一。生物制造业占美国国内生产总值的近2%，而且其比例还在扩大。许多生物制造涉及使用细胞来制造药物。这类药物的例子包括抗癌药物和疫苗。开发这些药物的一个关键因素是需要建立复杂的制造工艺。AMBIC将实施工程创新，以提高我国生产这些重要的延长生命和挽救生命的药物的能力。这些改进将在未来几十年提高美国生物制造业的竞争力，导致这些公司进行更多经济投资，并为美国工人提供更多就业机会。AMBIC的使命是开发使能技术、知识、设计工具和方法，应用和集成高通量和基于基因组的技术，以快速跟踪先进的生物制造过程。AMBIC是第一个致力于哺乳动物细胞培养上游开发的I/UCRC，专注于中国仓鼠卵巢(CHO)细胞，中国仓鼠卵巢(CHO)是工业的主要生物制药生产宿主。AMBIC将汇集专注于哺乳动物细胞培养制造的领先学术和工业生物技术专家，在竞争前的研究水平上解决生物制药制造中的复杂问题。这个多大学中心将使AMBIC能够利用各个地点许多教职员工的技能和专业知识。AMBIC将通过开展以下方面的研究，成为保持国家在生物制药生产领域卓越水平的关键催化剂：1)了解与工业相关的生物学(如全基因组学、生物信息学、过程和产品质量等)；2)过程监测和控制(如分析、仪器仪表、数据挖掘和建模)；3)共识和标准化问题(如标准、简单指纹、原材料问题、监管问题、法医生物处理、克隆)。通过系统级生物学分析、新型细胞系开发、生物反应器优化和先进分析，AMBIC将提供变革性的解决方案，可以降低生物制造成本并提高生物处理效率。最重要的是，这些进展最终可能有助于向需要的患者提供更多的生物药物，并降低消费者的整体医疗成本。此外，AMBIC将建立和维持一条受过教育并积极进取的多层次学生渠道，从事生物制药制造和开发方面的职业。与企业合作伙伴的合作将使学生能够解决该行业面临的最紧迫的问题。此外，该中心将致力于吸引和激励来自少数族裔群体的学生从事生命科学、工程或相关的STEM领域的职业生涯。AMBIC活动的一个重要部分，也是国际和平协会的一个坚定目标是，通过激励来自各种背景的学生了解通过STEM在生物技术和生物医学领域的职业生涯帮助他人的令人兴奋的机会，增加妇女和代表性不足的少数群体在STEM学科中的参与。

项目成果

Bigdata analytics identifies metabolic inhibitors and promoters for productivity improvement and optimization of monoclonal antibody (mAb) production process

大数据分析确定代谢抑制剂和促进剂，以提高生产率和优化单克隆抗体 (mAb) 生产流程

• DOI: 10.1186/s40643-020-00318-6
• 发表时间: 2020
• 期刊: Bioresources and Bioprocessing
• 影响因子: 4.6
• 作者: Morris, Caitlin;Polanco, Ashli;Yongky, Andrew;Xu, Jianlin;Huang, Zhuangrong;Zhao, Jia;McFarland, Kevin S.;Park, Seoyoung;Warrack, Bethanne;Reily, Michael
• 通讯作者: Reily, Michael

Integration of Time-Series Transcriptomic Data with Genome-Scale CHO Metabolic Models for mAb Engineering

将时间序列转录组数据与单克隆抗体工程的基因组规模 CHO 代谢模型相集成

• DOI: 10.3390/pr8030331
• 发表时间: 2020
• 期刊: Processes
• 影响因子: 3.5
• 作者: Huang, Zhuangrong;Yoon, Seongkyu
• 通讯作者: Yoon, Seongkyu

Modulation of nutrient precursors for controlling metabolic inhibitors by flux balance analysis

通过通量平衡分析调节营养前体以控制代谢抑制剂

• DOI: 10.1002/btpr.3313
• 发表时间: 2022
• 期刊: Biotechnology Progress
• 影响因子: 2.9
• 作者: Hoang, Duc;Kuang, Bingyu;Liang, George;Wang, Zhao;Yoon, Seongkyu
• 通讯作者: Yoon, Seongkyu

Identifying metabolic features and engineering targets for productivity improvement in CHO cells by integrated transcriptomics and genome-scale metabolic model

• DOI: 10.1016/j.bej.2020.107624
• 发表时间: 2020-07-15
• 期刊: BIOCHEMICAL ENGINEERING JOURNAL
• 影响因子: 3.9
• 作者: Huang, Zhuangrong;Yoon, Seongkyu
• 通讯作者: Yoon, Seongkyu

Characterization of Chinese hamster ovary cell culture feed media precipitate

• DOI: 10.1002/btpr.3188
• 发表时间: 2021-07-02
• 期刊: BIOTECHNOLOGY PROGRESS
• 影响因子: 2.9
• 作者: Hoang, Duc;Galbraith, Shaun;Yoon, Seongkyu
• 通讯作者: Yoon, Seongkyu