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）资助的。0853948/0853869 Chen/Cramer化学和生物分离项目的NSF奖项支持了Wilfred Chen教授和Steven M. Cramer分别在加州大学、滨江和伦斯勒理工学院，产生了一组新的热响应性弹性蛋白样蛋白（ELP）-IgG结合结构域融合物，作为捕获支架用于抗体的直接纯化和回收。这里提出的可调捕获支架扩展了自然界的想法，朝着全新的目标发展。刺激响应性ELP所表现出的可调疏水相互作用被专门定制为直接从复杂混合物中可逆捕获抗体的非共价方法。最终结果是一个新的集成平台，通过消除任何色谱步骤，大大简化了抗体纯化的整个过程，并降低了与下游纯化相关的成本。这些新型捕获支架的实际效用将与百时美施贵宝（BMS）合作进行大规模工业抗体纯化。这将使这些捕获支架与工业相关的抗体原料的评估，并将使工作能够进行，这将是不可能没有这种学术/工业合作。BMS已同意提供分析方法和扩大规模方面的必要培训，并将允许研究生在BMS内部开展部分工作。拟议的研究将对用于蛋白质纯化的智能生物聚合物及其在工业环境中的实施产生重大影响。新型ELP融合体的开发将使得表达水平显著增加，同时还建立期望的转变温度和盐条件。此外，这些融合将使得能够以高产品质量相对温和地洗脱抗体。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，学术界和工业界之间的这种独特合作将作为抗体纯化这一变革性技术的工业实施的概念验证研究。此外，参与这项研究的研究生将获得连接生物化学，现代遗传学和工艺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.