Reversible assembly/disassembly of DNA frames and applications in logic design, ratiometric sensing and bioimaging

Abstract

Molecular computing holds great promise for intelligent diagnosis and treatment of diseases at molecular level, thus designing molecular logic gates to operate programmably and autonomously for molecular analysis is urgently needed. In this work, controllable assembly/disassembly of DNA tetrahedron, a typical DNA frame structure, was achieved by alternate addition of two stimulating factors including nucleic acid and antisense nucleic acid, Hg2+ and cysteine, or H+ and OH−. Such a DNA frame structure assembly/disassembly behavior had been proved to be reversible and could be cycled for several times, which was clearly reflected by repeated switch-on and switch-off of the fluorescence resonance energy transfer signal. Based on this principle, three binary INHIBIT logic gates were constructed by using different input combinations. Such a principle was also successfully used to develop various sensing systems for the ratiometric detection of microRNA, Hg2+, cysteine and pH. Thanks to the highly efficient internalization of DNA nanostructures by cells, the proposed sensing systems were demonstrated to work well for the ratiometric imaging of microRNA, Hg2+ and pH value in living cells.