Aptamers are RNA or DNA molecules selected in vitro from vast populations of random sequence that recognize specific ligands by forming binding pockets. Allosteric ribozymes are RNA enzymes whose activity is modulated by the binding of an effector molecule to an aptamer domain, which is located apart from the active site. These RNAs act as precision molecular switches that are controlled by the presence or absence of a specific effector.

Researchers in the Breaker lab have developed molecular switches in several ways using either modular rational design or in vitro selection of communication modules. These methods permit scientists to fuse independently-functioning units into multi-functional molecules. We have created ribozymes that respond to ATP, metal ions, and small biological compounds such cGMP, theophylline, and FMN. In addition, we have used allosteric selection to generate new aptamers. Allosteric selections link the evolution of the new aptamer to ribozyme function. In this way, we have discovered aptamers for the second messengers cAMP and cGMP and for a variety of metal ions. In addition, it has been possible to change the specificity of a known RNA aptamer by allosteric selection to recognize a related compound more readily.