Nature utilizes specific interactions between nucleic acids, proteins, and small molecules to direct all of the biological processes that make life possible. Inspired by these molecular recognition capabilities, the aim of our research program is twofold: (1) to engage in hypothesis driven research towards a deeper understanding of the forces that drive small molecule-nucleic acid and nucleic acid-nucleic acid interactions (2) to apply our understanding of these interactions towards the development of new technologies in biosensing, bioimaging, and antisense therapeutics.
We have recently demonstrated the use of a split aptamer to transduce a small molecule signal (in this case cocaine) into the output of DNA ligation. If present in solution, cocaine directs assembly of the split aptamer, bringing DNA-appended reactive groups into close proximity and thus promoting a chemical ligation. The ligation chemistry utilized is strain-promoted azide-alkyne cycloaddition, as azides and cyclooctynes are orthogonal to common biological functional groups and the reaction does not require exogenous reagents. Research is underway to utilize this technology for the development of small-molecule detection assays.
Peptide nucleic acid (PNA) is a nucleic acid analog in which the phosphodiester backbone is replaced with a peptide-like aminoethylglycine unit. PNA shows great potential for use in antisense and cellular imaging applications due to its higher affinity and selectivity for native nucleic acids as well as its increased resistance to degradation by nucleases and proteases. In order to expand the role of PNA in these applications, we are working to modify the backbone and investigate the subsequent effects on binding with DNA and RNA. Additionally, our research is aimed at improving cellular delivery of PNA through conjugation with nanoparticles. We anticipate that this research will produce PNA having improved pharmacokinetics as well as new capabilities as a therapeutic and imaging agent.
Programmable materials capable of autonomous information processing can be generated by the fusion of a readable code to an output-producing functional material, and carries potential for use in applications including computing, biosensing, and nanotechnology. Our research aims to synthesize DNA-crosslinked micelles (DCMs) as a novel type of programmable materials capable of stimuli-responsive assembly and disassembly.