Catalyst‐Accelerated Circular Cascaded DNA Circuits: Simpler Design, Faster Speed, Higher Gain

Abstract

DNA cascaded circuits have great potential in detecting low abundance molecules in complex biological environment due to their powerful signal amplification capability and nonenzymatic feature. However, the problem of the cascaded circuits is that the design is relatively complex and the kinetics is slow. Herein, a new design paradigm called catalyst‐accelerated circular cascaded circuits is proposed, where the catalyst inlet is implanted and the reaction speed can be adjusted by the catalyst concentration. This new design is very simple and only requires three hairpin probes. Meanwhile, the results of a series of studies demonstrate that the reaction speed can be accelerated and the sensitivity can be also improved. Moreover, endogenous mRNA can also be used as a catalyst to drive the circuits to amplify the detection of target miRNA in live cells and in mice. These catalyst‐accelerated circular cascaded circuits can substantially expand the toolbox for intracellular low abundance molecular detection.

A two-layer circuit cascade-based DNA machine for highly sensitive miRNA imaging in living cells

“…26,27 Compared with linear amplification of a single DNA circuit for the input target, the cascaded DNA circuits amplify signals polynomially and exponentially, thus achieving extraordinary amplification efficiency and further improving the detection sensitivity. 28,29 For example, the Ellington group has developed a cascaded CHA-based amplifier that yielded 7000-fold signal amplification. 30,31 Liang et al implemented cascaded DNA circuits for the catalytic self-assembly of spherical nucleic acids with 100 000-fold signal amplification.…”

Enzyme-Accelerated Catalytic DNA Circuits Enable Rapid and One-pot Detection of Bacterial Pathogens

“…However, conventional catalytic DNA circuits have the drawbacks of low reaction depth and slow kinetics, leading to long reaction times and inferior sensing performance. To address these issues, various strategies have been developed, such as (i) constructing concatenated [19,20] or auto-closed [21][22][23] ampli cation methods by integrating different catalytic circuits or selffeedback autocatalytic approaches within same DNA circuits [24][25][26] for improving the depth of reaction, (ii) utilizing polymers [27][28][29] or spatial-con nement scaffolds [30][31][32] to concentrate reactants for accelerating kinetics, and ( ) creating reactant recycling circuits by adding additional DNA reactants [33,34] or protein enzymes [35,36]. Strategies that integrate multiple DNA strands or extend long sequences from the original structure of reactants need a more complex design, which may confront high signal leakage caused by non-speci c interactions among reactants.…”