Synthetic biology tools to promote the folding and function of RNA aptamers in mammalian cells

RNA aptamers are structured RNAs that can bind to diverse ligands, including proteins, metabolites, and other small molecules. RNA aptamers are widely used as in vitro affinity reagents. However, RNA aptamers have not been highly successful as bioactive intracellular molecules that can bind target molecules and influence cellular processes. We describe how poor RNA aptamer expression and especially poor RNA aptamer folding have limited the use of RNA aptamers in RNA synthetic biology applications. We discuss innovative new approaches that promote RNA aptamer folding in living cells and how these approaches have improved the function of aptamers in mammalian cells. These new approaches are making RNA aptamer-based synthetic biology and RNA aptamer therapeutic applications much more achievable.