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.
