Nucleic Acids as Probes and Sensors

The discovery of the double-helical structure of DNA forms the cornerstone of our understanding of nucleic acid metabolism and has spurred tremendous growth in biochemical technology. Specifically, the ability of nucleobases to form precise and programmable bonds with each other has led to a vast amount of research on synthetic nucleic acid analogues that can exercise similar binding characteristics on their natural counterparts. (a) Probes: We have explored one such analog, peptide nucleic acids (PNA) for their ability to overcome unusual DNA structures called quadruplexes, and have in the process discovered a non-Watson Crick mode of binding PNA to DNA targets.  (b) Sensors: The polymeric characteristics of oligonucleotides (DNA and RNA) have been utilized for creation of special sequences called aptamers that bind specific target molecules with high affinity and specificity. A prominent theme of our research is the exploration of general methods that do not require labeled oligonucleotide aptamers. We have developed signaling strategies that avoid or minimize synthetic modification of aptamers with the ultimate goal of creating selective, sensitive yet simple and cheap assays.