Non-technical: This award by the Biomaterials program in the Division of Materials Research to University of Georgia is to develop a platform for antibody mimetics by scaffolding peptides on single stranded DNA. This award is cofunded by the Genetic Mechanisms program in the Division of Molecular & Cellular Biosciences in the Directorate for Biological Sciences. Antibodies are essential to facilitating discoveries in biomedical research; however, they have a variety of shortcomings that have elicited concerns over accessibility to high-quality antibodies for biomedical research. Alterative and more robust polymers for molecular recognition are needed to drive discovery efforts forward. Nucleic acid polymers have demonstrated immense promise as high-affinity reagents; however, their lack of chemical functionality limits their ability to compete with proteins as receptors. By merging the evolvable molecular scaffold of nucleic acid polymers with diverse protein functionality, the PI aims to evolve a new class of antibody mimetics for biomedical research, which may address the critical deficit of available antibodies for molecular targets. These research efforts will be coupled with educational and training outreach at the high school, undergraduate, and graduate levels in order to assist in the development of a future generation of scientists that are properly equipped to tackle interdisciplinary research problems.
This proposal describes research to develop an in vitro selection platform for antibody mimetics by scaffolding peptides on DNA. Nucleic acid aptamers have provided numerous advantages over traditional antibodies; however, their functional group deficit limits their potential to match the performance of proteinogenic affinity reagents. By merging the evolvable molecular scaffold of nucleic acid polymers with protein functionality, this investigator will use this class of polymers to mimic the hetero- and multivalent approach nature uses at protein-protein interfaces. The investigator will use an enzymatic strategy to sequence-specifically incorporate unique peptide fragments along a DNA template. This approach will enable the concomitant evolution of the ssDNA scaffold and the identity of the displayed peptides to achieve molecular recognition of protein targets. If successful, this new class of biomimetic polymers could aid in addressing the deficit of high-affinity reagents for biomedical research. These research efforts will be coupled with educational and training outreach at the high school, undergraduate, and graduate levels.
