A rational design of a cascaded DNA circuit for nanoparticle assembly and its application in the discrimination of single-base changes

In the field of dynamic DNA nanotechnology, a designable DNA assembly circuit based on the toehold-mediated strand displacement reaction has demonstrated its ability to program the self-assembly of nanoparticles. However, the laborious work for the modification of nanoparticles with oligonucleotides, the long assembly time, and the circuit leakage prevent its further and scalable applications. To this end, cascaded circuits composed of two recycling circles are rationally designed in this study. Through the pre-initiation of the autonomous reaction, nanoparticles as sensing elements and no additionally exposed bases on the substrate hybridized with fuel strand, the real assembly time and signal leakage for diagnostic application can be effectively reduced and eliminated, thus offering a promising methodology for future point-of-care testing.