RNAs perform a diverse array of catalytic and regulatory functions in viruses and cells and are becoming increasingly important disease biomarkers and drug targets. RNA structures are mainly stabilized by base paired double-stranded (ds) stem regions. Together with single-stranded (ss) loop regions, RNAs can fold into complex secondary and tertiary structures, facilitating the molecular recognition of RNA structures by small molecules and peptides/proteins. Currently, programmable RNA structure-specific and tight-binding ligands are relatively unexplored. Peptide nucleic acid (PNA) is characterized by a neutral, peptide-like backbone, with superior chemical stability and strong binding to complementary RNA/DNA sequences. Importantly, PNAs conjugated with cell-penetrating moieties show promising bioactivities in animal models. In this presentation, I will present our results on the synthesis and biophysical characterization of the novel chemically-modified dsRNA-binding PNAs (dbPNAs), which show selective recognition of dsRNAs over ssRNAs and dsDNAs in a sequence-specific manner. I will discuss the applications of the PNAs platform in targeting a miRNA hairpin precursor, a tau pre-mRNA splice site hairpin structure, and an influenza viral RNA structure.

Dr. Gang CHEN received his B.S. degree in Chemistry at the University of Science and Technology of China (USTC) in 2001. He did his Ph.D. studies with Prof. Douglas TURNER in the Department of Chemistry at the University of Rochester. His Ph.D. work involved thermodynamic and NMR studies of RNA internal loops. A better understanding of the sequence dependence of thermodynamics for RNA structures will improve the accuracy of the RNA secondary structure prediction programs such as MFOLD and RNAstructure. He earned his Ph.D. in 2005. He was a postdoctoral fellow in Prof. Ignacio TINOCO’s lab in the Department of Chemistry at the University of California, Berkeley from January 2006 to June 2009. His research in Tinoco lab was on single-molecule mechanical unfolding and folding of RNA pseudoknots by laser optical tweezers, which provided new insights into ribosomal reading-frame regulation by cis-acting mRNA structures. He was a Research Associate in Prof. David MILLAR's lab in the Department of Molecular Biology at The Scripps Research Institute working on HIV-1 Rev-RRE assembly using single-molecule fluorescence techniques. In July 2010, he joined the faculty in the Division of Chemistry and Biological Chemistry at Nanyang Technological University in Singapore.