Designing oligonucleotide conformational states for quantitative transcription factor detection (768.2)

Abstract

Nucleic acids undergo dynamic conformational rearrangements that have enabled a variety of bio‐sensors, biologically‐inspired probes with applications from real‐time PCR to the detection of small molecules. Understanding the forces that drive these rearrangements enables more sophisticated and accurate bio‐sensors. Transcription factor beacons (TF beacons) are versatile, nucleic acid‐based optical bio‐sensors that report the concentration of TFs. As many cancers over‐express oncogenic TFs, optimizing tools for early detection of these biomarkers would improve diagnosis of early‐stage cancers. We have investigated how changing the thermodynamic and kinetic stability of TF beacons’ ground state conformations and excited state conformations enable tuning of sensitivity and detection limit. To aid this process, and for wider adoption of TF beacons, we have developed web servers for the automated design of TF beacons against arbitrary protein targets. Ultimately, better understanding of nucleic acid conformational changes and stability enables the development of efficacious bio‐sensors with a range of applications, including detecting TF level changes in patient samples for earlier point‐of‐care diagnosis.