SBIR Phase II: Multivariate Analysis of Heterologous Protein Expression

SBIR II 期：异源蛋白表达的多变量分析

• 批准号: 0750206
• 负责人: Mark Welch
• 金额: $ 50万
• 依托单位: DNA Twopointo Inc
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-15 至 2013-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0750206&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Multivariate; Analysis

This SBIR Phase II research develops methods to improve the manufacture of recombinant protein products produced in foreign hosts. Cost-effective production of proteins generally utilizes organisms that are well-suited for protein engineering and large-scale production. Establishing a suitable production system for a protein is often a time-consuming, trial-and-error-based process and can be a significant barrier for the commercialization of a protein. In cases where production systems are found, they are often far from optimized due to the time and cost required as well as our current limited understanding of the critical parameters. In Phase I several gene design variables were assessed for their importance to protein expression in the bacterium Escherichia coli, a commonly used production organism. Data suggested novel means for gene optimization that were unexpected from conventional wisdom. In Phase II relevant gene design variables suggested by Phase I will be explored toward development of a refined model of the relationship of gene design to protein expression in E. coli as well as in other useful production organisms.The broader impacts of this research are improved manufacturing techniques for recombinant protein based products. Protein products constitute a currently $40 billion and rapidly growing world-wide market including industrial enzymes, diagnostic enzymes and protein pharmaceuticals. The tools developed from this project will drastically improve the speed, reduce the cost, and remove the uncertainties of modern protein manufacturing, which significantly limit this market. Improved production will also accelerate the study of proteins with therapeutic or otherwise marketable potential, expanding the field of candidate proteins for commercialization.

这项SBIR II期研究开发了改进在国外宿主中生产的重组蛋白产品的方法。 具有成本效益的蛋白质生产通常利用非常适合蛋白质工程和大规模生产的生物体。 为蛋白质建立合适的生产系统通常是一个耗时的、基于试错的过程，并且可能是蛋白质商业化的重大障碍。 在发现生产系统的情况下，由于所需的时间和成本以及我们目前对关键参数的有限理解，它们通常远未优化。在第一阶段，几个基因设计变量的重要性进行了评估，蛋白质表达的细菌大肠杆菌，一种常用的生产生物。 数据表明，基因优化的新方法是传统智慧所意想不到的。 在第二阶段，将探讨第一阶段提出的相关基因设计变量，以建立一个精确的基因设计与大肠杆菌蛋白质表达之间关系的模型。这项研究的更广泛的影响是改进了基于重组蛋白的产品的制造技术。 蛋白质产品构成了目前400亿美元的快速增长的全球市场，包括工业酶，诊断酶和蛋白质药物。从该项目开发的工具将大大提高速度，降低成本，并消除现代蛋白质制造的不确定性，这些不确定性极大地限制了这个市场。 改进的生产也将加速具有治疗或其他可销售潜力的蛋白质的研究，扩大商业化候选蛋白质的领域。