Screening and implementing universal ligands for immunoglobulins

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The human body produces antibodies, also known as immunoglobulins, to recognize and respond to specific pathogens, including bacteria and viruses. Synthetic production of high quality antibodies is a means to treat disease via immunotherapy. The use of synthetic antibodies in commercial kits continues to grow. The handling and purification of antibodies is thus crucial to commercial manufacturing of therapeutics. Current technology uses bacteria-derived proteins that bind to the antibodies as a means to capture and purify the antibody. However, these proteins are costly and the process typically requires harsh chemical solvents. In certain cases, the harsh chemicals lead to irreversible damage of the desired antibody product. This project seeks to develop DNA-derived molecules (oligonucleotides) that have programmable antibody capture and release, yet do not compromise the therapeutic function of the antibodies, and employ environmentally-friendly processing steps. This project strives to identify and implement oligonucleotide-based ligands for antibody capture. Trainees on this project will employ a multidisciplinary approach spanning engineering, biology, and immunology to both (i) screen and identify effective antibody-binding ligands that do not compromise antibody quality and (ii) discover structure-binding relationships in the ligand-antibody systems that can, in turn, inform screening efforts. Successful identification and implementation of these ligands or affinity reagents for immunologlobulins address a growing demand for identifying new, robust, cost-effective and sustainable technological approaches. Moreover, these oligonucleotide-based ligands can potentially shorten the time-to-market for the ever expanding supply of new polyclonal, monoclonal, and modified antibodies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.