Nucleic acid based tools for pharmacology and nano-engineering

We have developed modular assays based on aptamer displacement or protein-dependent reporter ribozymes for the screening of small molecule inhibitors. Thereby, chemical space can be explored in a rapid, focused, and modular manner, by indirectly taking advantage of the highest molecular diversity currently amenable to screening, namely that of 1016 different nucleic acid sequences. In this account, we discuss the application of these approaches to find new inhibitors for target proteins. Examples showing that these modulators can be used as tools for gaining novel biological insight are provided. We also discuss some recent data on interlocked DNA architectures such as entirely double-stranded DNA rotaxanes.