Developing RNA aptamers for potential treatment of neurological diseases

AMPA receptor antagonists are drug candidates for potential treatment of a number of CNS diseases that involve excessive receptor activation. To date, small-molecule compounds are the dominating drug candidates in the field. However, lower potency, cross activity and poor water solubility are generally associated with these compounds. Here we show the potential of RNA-based antagonists or RNA aptamers as drug candidates and some strategies to discover these aptamers from a random sequence library (∼10¹⁴ sequences). As an alternative to small molecule compounds, our aptamers exhibit higher potency and selectivity toward AMPA receptors. Because aptamers are RNA molecules, they are naturally water soluble. We also discuss the major challenges of translating RNA aptamers as lead molecules into drugs/treatment options.