Progress in Thioaptamer Development

Thioaptamers are thiophosphate ester modified nucleic acids that are isolated via in vitro or bead-based thioaptamer selection against a target molecule such as a protein. Thioaptamers offer advantages over traditional aptamers in their enhanced affinity and specificity and higher stability, largely due to the properties of the sulfur backbone-modifications. An in vitro thioaptamer selection procedure that simultaneously selects for sequence and optimized hybrid phosphoromonothioate or phosphate backbone substitutions is outlined. A novel bead-based thioaptamer selection protocol that can produce mixed phosphorodithioate, phosphoromonothioate or phosphate hybrid backbones is also described. Several examples of thioaptamers targeting specific protein are provided. Such thioaptamers are shown to modulate protein activity in vivo.