GOALI: Industrial Implementation of Smart Biopolymers for Antibody Purification

该奖项是根据2009年《美国复苏和再投资法案》(公法111-5)提供资金的。0853948/0853869陈/克拉默这项由化学和生物分离计划颁发的国家科学基金会奖支持了加州大学河滨分校的Wilfred Chen教授和伦斯勒理工学院的Steven M.Cramer教授的工作，他们创造了一套新的温度响应性弹性蛋白样蛋白-免疫球蛋白结合域融合，作为捕获支架，用于直接纯化和回收抗体。这里提出的可调捕捉脚手架扩展了来自自然的想法，走向了全新的目标。刺激响应型ELP表现出的可调的疏水相互作用是专门作为一种非共价方法定制的，可以直接从复杂的混合物中可逆地捕获抗体。最终结果是一个新的集成平台，通过省去任何层析步骤，大大简化抗体纯化的整个过程，并改善与下游纯化相关的成本。这些新型捕获支架的实际实用性将与百时美施贵宝(BMS)合作评估，用于大规模工业抗体纯化。这将使使用工业相关抗体原料对这些捕获支架进行评估成为可能，并将使没有这种学术/工业合作就不可能开展的工作得以开展。BMS已同意提供必要的分析方法培训和扩大规模，并将允许研究生在BMS内部开展部分工作。这项拟议的研究将对用于蛋白质纯化的智能生物聚合物的技术水平及其在工业环境中的实施产生重大影响。新型ELP融合蛋白的开发将使表达水平显著提高，同时也建立了理想的过渡温度和盐条件。此外，这些融合将能够相对温和地洗脱高质量的抗体。如果成功，开发的方法将能够有效和简单地回收抗体，并将降低整体制造复杂性和相关成本。重要的是，学术界和产业界之间的这种独特的合作将作为这一变革性抗体纯化技术的工业实施的概念研究的证明。此外，参与这项研究的研究生将获得连接生物化学、现代遗传学和过程工程的重要接口和协同作用的综合视角。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). 0853948/0853869 Chen/Cramer This NSF award by the Chemical and Biological Separations program supports work by Professors Wilfred Chen and Steven M. Cramer at University of California, Riverside and Rensselaer Polytechnic Institute, respectively, to generate a new set of thermo-responsive elatin-like-protein (ELP)-IgG-binding domain fusions as the capturing scaffolds for the direct purification and recovery of antibodies. The tunable capturing scaffolds proposed here extends on ideas from nature toward entirely new objectives. The tunable hydrophobic interaction exhibited by the stimuli-responsive ELP is tailored specifically as a non-covalent method to reversibly capture antibodies directly from a complex mixture. The end result is a new integrated platform that will greatly simplify the overall process of antibody purification by eliminating any chromatographic step and improve the cost associated with down-stream purification. The practical utility of these novel capturing scaffolds will be evaluated for large-scale industrial antibody purification in partnership with Bristol-Myers Squibb (BMS). This will enable the evaluation of these capturing scaffolds with industrially relevant antibody feed stocks and will enable work to be carried out that would not be possible without this academic/industrial collaboration. BMS has agreed to provide the necessary training in the analytical methods and scale-up and will allow the graduate students to carry out a portion of their work in-house at BMS. The proposed research will have a significant impact on the state of the art of smart biopolymers for protein purification and their implementation in an industrial setting. The development of novel ELP fusions will enable significant increases in expression level while also establishing desirable transition temperatures and salt conditions. Further, these fusions will enable relatively gentle elution of antibodies with high product quality. If successful, the developed method will enable efficient and simple recovery of antibodies and will reduce the overall manufacturing complexity and associated costs. Importantly, this unique collaboration between academia and industry will serve as a proof of concept study for the industrial implementation of this transformative technology for antibody purification. Moreover, graduate students participating in this research will gain an integrated perspective of the important interfaces and synergies connecting biochemistry, modern genetics, and process engineering.