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A controllable nanodevice actuated by stimulus-responsive module.

Toehold-mediated strand displacement is widely used to construct and operate DNA nanodevices. Cooperative regulation of strand displacement with diverse factors is pivotal in the design and construction of functional and dynamic devices. Herein, a cofactor-assisted three-way DNA junction-driven strand displacement strategy was reported, which could tune the reaction kinetics by the collaboration of DNA and other types of stimulus. This strategy is responsive to various inputs by incorporation of the specific sequence into the three-way junction structure. Specifically, the cooperation of multiple factors changes the conformation of the specific domain and promotes the reaction. To demonstrate the strategy, adenosine triphosphate (ATP), HG2+, and pH were used as cofactors to modulate the displacement reaction. The electrophoresis and fluorescence experiments showed that the cooperative regulation of the strand displacement reaction could be achieved by diverse factors using this strategy. The proposed strategy provides design flexibility for dynamic DNA devices and may have potential in biosensing and biocomputing.

The precursors of functional biomolecules in living cells are synthesized in a bottom-up manner and subsequently activated by modification into a delicate structure with near-atomic precision. DNA origami technology provides a promising way to mimic the synthesis of precursors, although mimicking the modification process is a challenge. Herein, a DNA paper-cutting (DNA kirigami) method to trim origami into designer nanostructures is proposed, where the modification is implemented by a polymerase-triggered DNA strand displacement reaction. Six geometric shapes are created by cutting rectangular DNA origami. Gel electrophoresis and atomic force microscopy results demonstrate the feasibility and capability of the DNA paper-cutting method. The proposed DNA paper-cutting strategy can enrich the toolbox for dynamically transforming DNA origami and has potential applications in biomimetics. .

Toehold-mediated DNA strand displacement endows DNA nanostructures with dynamic response capability. However, the complexity of sequence design dramatically increases as the size of the DNA network increases. We attribute this problem to the mechanism of toehold-mediated strand displacement, termed exact strand displacement (ESD), in which one input strand corresponds to one specific substrate. In this work, we propose an alternative to toehold-mediated DNA strand displacement, termed fuzzy strand displacement (FSD), in which one-to-many and many-to-one relationships are established between the input strand and the substrate, to reduce the complexity. We have constructed four modules, termed converter, reporter, fuzzy detector, and fuzzy trigger, and demonstrated that a sequence pattern recognition network composed of these modules requires less complex sequence design than an equivalent network based on toehold-mediated DNA strand displacement.

We propose synthetic DNA/RNA transcription circuits based on specific aptamer recognition. By mimicking transcription factor regulation, combined with specific enzyme/DNA aptamer binding, multiple biomolecules including DNA, RNA, polymerase, restriction enzymes and methylase were used as regulators. In addition, multi-level cascading networks and methylation-switch circuits were also established. This regulation strategy has the potential to expand the toolkit of in vitro synthetic biology.

Inflammasomes are involved in gut homeostasis and inflammatory pathologies, but the role of NLRP3 inflammasome in these processes is not well understood. Cryopyrin-associated periodic syndrome (CAPS) patients with NLRP3 mutations have autoinflammation in skin, joints, and eyes, but not in the intestine. Here we show that the intestines of CAPS model mice carrying an Nlrp3 R258W mutation maintain homeostasis in the gut. Additionally, such mice are strongly resistant to experimental colitis and colorectal cancer; this is mainly through a remodelled gut microbiota with enhanced anti-inflammatory capacity due to increased induction of regulatory T cells (Tregs). Mechanistically, NLRP3R258W functions exclusively in the lamina propria mononuclear phagocytes to directly enhance IL-1β but not IL-18 secretion. Increased IL-1β boosts local antimicrobial peptides to facilitate microbiota remodelling. Our data show that NLRP3R258W-induced remodelling of the gut microbiota, induces local Tregs to maintain homeostasis and compensate for otherwise-detrimental intestinal inflammation., Inflammasomes are involved in gut homeostasis and inflammatory pathologies. The authors show that a hyperactive NLRP3 inflammasome maintains gut homeostasis through remodelling of the gut microbiota and induction of regulatory T cells.