Aptamers and aptazymes: accelerating small molecule drug discovery

Synthetic nucleic acid ligands, known as aptamers, are versatile tools that can greatly enhance the efficiency of modern drug development. Exhibiting binding characteristics comparable to or even better than monoclonal antibodies, these ligands can be used as detection probes, highly efficient inhibitors of protein function or specific competitors in high-throughput screening (HTS) assays. Thus, aptamer technology can be exploited to address the growing demand for multi-parallel analysis of proteomes, functional prioritization of potential drug targets and accelerated small molecule lead identification. The unique advantages of this technology are the rapid automated generation of sophisticated ligands against almost any target molecule and the convenient structural or chemical modification of the nucleic acid probes. Depending on the strategy, an RNA aptamer can be expressed transgenically to investigate and inactivate an endogenous protein in an animal model, or it can be designed to function as a highly sensitive nucleic acid biosensor. More recently, the technology has been extended to directly link functional target validation with HTS, accelerating the process of drug discovery.