| Description |
Deoxyribonucleic acid (DNA) provides many exciting functions outside of simply encoding genetic information. Herein, we report two techniques to control the assembly and disassembly of nucleic acids. Within these techniques, DNA is used as a programmable material for biosensing and drug delivery. In chapter 1, we report an effort to create a quantitative Polymerase Chain Reaction (qPCR)-compatible split aptamer assay. Split aptamers are single-stranded DNA molecules that reversibly assemble in the presence of a target molecule, which promotes reactivity by increasing the effective reactive group concentrations during aptamer assembly. Currently, our lab has pioneered the development of this technique, referred to as Split Aptamer Proximity Ligation (StAPL) technology, for small molecule detection. Previous techniques are limited due to the incompatibility of ligated backbones with qPCR amplification techniques, thus rendering this approach to quantification impractical. The goal of our research is to rectify this limitation and expand the scope of split aptamer chemistry using a triazole mimic of the phosphodiester backbone reported by Brown and coworkers, which would allow for real-time detection and quantification of small molecule targets. In chapter 2, we describe the application of nucleic acids to drive the formation of micelles for use as a programmable material for small molecule detection and responsive drug delivery. Micelles are spherical structures composed of amphiphilic monomers, which arrange their hydrophobic and hydrophilic regions to minimize contact between their hydrophobic sections with hydrophilic solvents. As result, micelles contain a hydrophobic pocket that can be used for hydrophobic drug delivery. However, this application is limited by the fact that guest molecules contained within the micelle are in equilibrium with the surroundings, thus allowing them to diffuse out, and micelles also dissociate at low monomer concentrations. We propose that DNA-erosslinking will increase micelle stability, allowing for guest molecule transport at lower concentrations of micelles without drug diffusion. DNA-crosslinking also allows for micelle disassembly control in response to environmental stimuli. Our current research efforts focus on generating and characterizing DNA-crosslinked micelles (DCM) by creating monomers comprised of DNA and hydrophobic polymer for biosensing and drug delivery. |
