A localized DNA finite-state machine with temporal resolution

Abstract

The identity and timing of environmental stimulus play a pivotal role in living organisms in programming their signaling networks and developing specific phenotypes. The ability to unveil history-dependent signals will advance our understanding of temporally regulated biological processes. Here, we have developed a two-input, five-state DNA finite-state machine (FSM) to sense and record the temporally ordered inputs. The spatial organization of the processing units on DNA origami enables facile modulation of the energy landscape of DNA strand displacement reactions, allowing precise control of the reactions along predefined paths for different input orders. The use of spatial constraints brings about a simple, modular design for the FSM with a minimum set of orthogonal components and confers minimized leaky reactions and fast kinetics. The FSM demonstrates the capability of sensing the temporal orders of two microRNAs, highlighting its potential for temporally resolved biosensing and smart therapeutics.

DNA nanotechnology-empowered finite state machines

“…This FSM allowed precise control of the reactions along predefined paths on the DNA origami structure for different input orders, resulting in minimized leakage and fast kinetics. 61 Some strategies demonstrated FSMs enabling rearrangement of other functional materials (e.g., metal nanoparticles) based on SDR-mediated DNA structural reconfigurations. For example, Kuzyk et al reported a DNA-fueled reconfigurable three-dimensional plasmonic metamolecule.…”

“…In another example, the DNA origami-based FSM was used to sense the temporal orders of two miRNAs (miR21 and miR122), which suggests the potential of DNA FSMs for temporally resolved biosensing and smart therapeutics. 61 Another important challenge in molecular sensing is to achieve high precision and multiplexity in complex physiological environments. Molecular probes generating switchable signals in response to specific cues are desired for such applications.…”

“…47,85,86 Although still challenging, there has been some progress in suppressing the leakage and crosstalk that limit the scale-up. 61,[85][86][87][88][89][90] Another promising approach is to utilize DNA selfassembly/disassembly systems, [91][92][93][94] which in theory can generate an infinite variety of distinct structures, thus might implement computing machines with almost infinite states.…”

“…This FSM allowed precise control of the reactions along predefined paths on the DNA origami structure for different input orders, resulting in minimized leakage and fast kinetics. 61…”

“…In another example, the DNA origami-based FSM was used to sense the temporal orders of two miRNAs (miR21 and miR122), which suggests the potential of DNA FSMs for temporally resolved biosensing and smart therapeutics. 61…”