Fig. 1.

(A) Full-length, folded aptamers sometimes support E-AB signaling, albeit typically with only rather modest changes in signaling upon target binding.⁹,²² Several approaches have been reported, however, by which aptamers can be engineered to undergo large-scale, binding-induced conformational changes that significantly improve E-AB signaling.²⁶,²⁷ These approaches include (B) the destabilization of the wild type aptamer via introduction of sequence truncations or point mutations, (C) the introduction of antisense sequences, or (D) the introduction of long unstructured sequences internal to the aptamer. The overarching goal of each of these approaches is to create an alternative structure in equilibrium with the “native”, target-binding fold such that the presence of the target pushes the equilibrium back to this native fold.