Precise Cross-Dimensional Regulation of the Structure of a Photoreversible DNA Nanoswitch

Abstract

In this study, an accurately and digitally regulated allosteric nanoswitch based on the conformational control of two DNA hairpins was developed. By switching between UV irradiation and blue light conditions, the second molecular beacon (H#2) would bind/separate with a repression sequence (RES) via the introduced PTG molecules (a photosensitive azobenzene derivative), resulting in the target aptamer sequence in the first molecular beacon (H#1) not being able/being able to hold the stem-loop configuration, hence losing/regaining the ability to bind with the target. Importantly, we successfully monitor conformation changes of the nanoswitch by an elegant mathematical model for connecting K i (the dissociation constant between RES and H#2) with K d (the overall equilibrium constant of the nanoswitch binding the target), hence realizing “observing” DNA structure across dimensions from “structural visualization” to digitization and, accurately, digitally regulating DNA structure from digitization to “structural visualization”.

Advances in Application of Azobenzene as a Trigger in Biomedicine: Molecular Design and Spontaneous Assembly

“…Dong and co‐workers [ 232 ] used an azobenzene to control the conformation of two DNA hairpins and constructed a light‐triggered allosteric nanoswitch ( Figure a). When a DNA hairpin (noted as H#1) contains a single‐stranded DNA aptamer sequence and presents a stem‐loop configuration, it is allowed to combine with a thrombin DNA aptamer.…”

“…a–c) Reproduced with permission. [ 232 ] Copyright 2019, American Chemical Society. d) Reproduced with permission.…”

Light responsive nucleic acid for biomedical application

“…Wang and coworkers [ 120 ] developed an allosteric DNA nanoswitch that controls thrombin activity through changes in the structure of two DNA hairpins. As shown in Figure 11B, the nanoswitch is mainly composed of two tail‐to‐tail DNA hairpins.…”

A nicking enzyme-assisted allosteric strategy for self-resetting DNA switching circuits

“…To simplify the complexity of system design, researchers have developed various DNA switching circuits with recyclable state transitions. [38][39][40][41][42][43][44][45][46] However, in order to restore the switch to its initial state and achieve reusability, it requires the repeated manual addition of fuel. Therefore, how to achieve the dynamic self-restoration of switching circuits to simplify system design and realize complex information processing currently remains a major challenge.…”