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Emulating biological transcription using artificial synthetic circuits is a key challenge in advancing systems chemistry. This Review discusses synthetic transcription circuits that are dynamically triggered to drive switchable, dissipative, oscillatory and bistable reaction models, mimicking native processes. These circuits are proposed as critical machineries for sensing and theragnostics.

A tension-modulated DNA origami-based nanosensor, compatible with bulk biochemical analysis in cell lysates, is used to assess the force-induced interaction of proteins involved in cellular mechanotransduction.

Achieving truly continuous and precise analog calculations using DNA neural networks is challenging. Here, the authors develop a fully analog DNA neural network system called CALCUL, that performs highly accurate weighted-sum operations and can be recycled.

The development of DNA-based machines is transforming fields such as drug delivery and biosensing. Here, design strategies are discussed and key performance metrics — speed, force generation, efficiency and autonomy — are examined to provide insights into the future of DNA nanotechnology.

DNA nanotechnology, including DNA machines and devices for computing, is a rapidly expanding field of research. Here, the authors fabricate DNA catenane machines for the programmable arrangement of gold nanoparticle cargoes, and study their switchable spectroscopic features.

DNA computing systems face challenges in switching functions due to complex molecular redesigns. Here, the authors introduce a base Stacking-Mediated Allostery (SMALL) strategy enabling efficient function switching with minimal architecture changes (1-2 nucleotides), implemented across diverse logic operations and cellular gene regulation patterns.

A new DNA logic circuits architecture based on single-stranded logic gates and strand-displacing DNA polymerase requires less computation time and fewer DNA strands.

Current DNA-assembled nanophotonic devices can only reconfigure among random or few defined states. Here, the authors demonstrate a DNA-assembled rotary plasmonic nanoclock in which a rotor gold nanorod carries out directional and reversible 360° rotation transitioning among 16 well-defined configurations.

Although DNA nanotechnology has found many applications in developing functional structures, there has never been an independent device contained within a 3D crystal. Now, a self-assembled three-state device that can change the colour of its crystal by diffusion of DNA-ligated dyes has been reported, representing the potential to develop programmable nanomechanical devices.

Membrane budding plays pivotal roles in cellular processes, but a fully artificial system mimicking natural budding processes remains elusive. Here, the authors report a DNA origami-based membrane budding system that recapitulates key aspects of clathrin-mediated endocytosis without relying on components of cellular budding machineries.

A design approach for engineering wireframe DNA nanostructures, in which each vertex and line segment can be individually controlled, can be used to fabricate complex structures including quasicrystalline two-dimensional patterns and reconfigurable three-dimensional Archimedean solids.

Adding nanobodies into DNA computing has proven difficult due to there always on state. Here, the authors propose a spatial segregation-based molecular computing strategy to program nanobodies into DNA molecular computation and elucidate the kinetic mechanism of microenvironment-confined DNA molecular computation.

Molecular switches are ubiquitous in the biochemistry regulatory network. Here, the authors construct synthetic molecular switches controlled by DNA-modifying enzymes such as DNA polymerase and nicking endonuclease to control and cascade assembly and disassembly.

Artificial DNA photofluids exhibit dissipative life-like motion when fuelled by light in space and time, converting photoenergy into out-of-equilibrium structures on the macroscale.

DNA tiles lay the foundation for programmable self-assembly of diverse DNA nanostructures. Here, the authors present a set of T-shaped crossover DNA tiles for various 2D tessellation and nanoring reconfiguration.

This study presents DNA-origami biocatalytic modular nanocompartments for programmed regulation of protein unfolding and degradation. These artificial nanofactories augment reaction kinetics, improve enzyme performance and reduce off-target effects.

Dynamic nanopores are promising tools for various biomedical applications. Here, the authors report on a triangular DNA nanopore that can switch in-situ between contracted and expanded states and provide low-noise repeatable signals in molecular sensing.

A molecular automaton comprising antibodies and oligonucleotides evaluates cells in a Boolean manner by executing a chemical cascade on cell surfaces.

Simple assembly rules applied recursively in a multistage assembly process enable the creation of DNA origami arrays with sizes of up to 0.5 square micrometres and with arbitrary patterns.

Motors based on RNA-cleaving DNA enzymes can transport cadmium sulphide nanocrystals along single-walled carbon nanotubes.

Real-time atomic force microscopy can be used image the individual steps of a DNA motor as it moves, autonomously and at constant average speed, along a 100-nm track.

Kinesin motor proteins conjugated to DNA nanostructures can be used to assemble a network of microtubule tracks, and to control the loading, active concentration and unloading of cargo on this network, or trigger its disassembly.

Nanoscale robots made from DNA origami can dynamically interact with each other and perform logic computations in a living animal.

DNA-based T-motifs that can self-assemble into ring structures can be designed to self-replicate through toehold-mediated strand displacement reactions.

Contractile rings are formed from cytoskeletal filaments, specific crosslinkers and motor proteins during cell division. Here, authors form micron-scale contractile DNA rings from DNA nanotubes and synthetic crosslinkers, with both simulations and experiments showing ring contraction without motor proteins, offering a potential first step towards synthetic cell division machinery.

Various methods, using DNA, have been reported for the recording of biomolecular interactions, but most are either destructive in nature or are limited to reporting pairwise interactions. Here the authors develop DNA-based motors, termed ‘crawlers’, that roam around and record their trajectories to allow the examination of molecular environments.

Computational frameworks for structural dynamics are in continuous need of being developed. Here the authors present a a computational framework based on Langevin dynamics to analyze structural dynamics and reconfiguration of DNA assemblies, offering a rational method for designing responsive and reconfigurable DNA machines

Building synthetic protocells and prototissues hinges on the formation of biomimetic skeletal frameworks. Here, the authors harness simplicity to create complexity by assembling DNA subunits into structural frameworks which support membrane-based protocells and prototissues.

The heterogeneous and compartmentalized environments within living cells make it difficult to deploy theranostic agents with precise spatiotemporal accuracy. Zhao et al. demonstrate a DNA framework state machine that can switch among multiple structural states according to the temporal sequence of molecular cues, enabling temporally controlled CRISPR–Cas9 targeting in living mammalian cells.

A synthetic nanocarrier based on DNA origami chassis offers control over valency, orientation and spatial arrangement of antibodies for simultaneously engaging immune signalling pathways, checkpoint inhibition and targeted co-stimulation in anticancer immunotherapy in vivo.

Artificial molecular machines have captured the imagination of researchers, given their clear potential to mimic and influence human life. Here, the authors use a DNA cube framework for the design of a dice device at the nanoscale to reproduce probabilistic events in different situations such as equal probability, high probability, and low probability.

Responsive molecular machines can perform specific tasks triggered by environmental or chemical stimuli. Here, the authors show that antibodies can be used as inputs to modulate the binding of a molecular cargo to a designed DNA-based nanomachine, with potential applications in diagnostics and drug delivery.

The nanospace confinement of a magnetic nanoparticle within a porous cage, coupled with an encodable DNA clutch interface, enables a remotely powered and controlled rotary nanomotor that is autoresponsive to its microenvironment.

Mesoscale molecular assemblies on the cell surface integrate information and amplify signals. Here the authors integrate DNA nanotubes in a controlled manner with mammalian cells to act as sheer stress meters.

Investigation of spatial organization and relationships of biomolecules in cellular nanoenvironments is necessary to understand essential biological processes, but methodologically challenging. Here, the authors report cellular macromolecules-tethered DNA walking indexing (Cell-TALKING) to probe the nanoenvironments of DNA modifications around histone post-translational modifications, and explore the nanoenvironments in different cancer cell lines and clinical specimens.

Ligand-oligonucleotide interactions can integrate both small molecules and proteins into nucleic acid-based circuits. Here the authors design ligand-aptamer complexes to control strand-displacement reactions for versatile ligand transduction.

An autonomous DNA-origami nanomachine powered by the chemical energy of DNA-templated RNA-transcription-consuming nucleoside triphosphates as fuel performs rhythmic pulsations is demonstrated. In combination with a passive follower, the nanomachine acts as a mechanical driver with molecular precision.

A nanoscale DNA origami turbine is shown to perform mechanical rotation by directly harvesting transmembrane potential energy from an ion-concentration gradient across a solid-state nanopore. The direction of rotation is set by the designed chiral twist in the turbine’s blades.

Synthetic molecular systems require subtle control over their thermodynamics and reaction kinetics to implement features such as catalysis. Here the authors propose using mismatches in a DNA duplex to drive catalytic reactions forward whilst maintaining tight catalytic control.

A DNA nanodevice vaccine has been developed and utilized to stimulate a tumour-specific cytotoxic T lymphocyte response in vivo, leading to the inhibition of tumour growth as well as prevention of metastasis.

In contrast to conventional thermal annealing approaches, the authors report on the self-assembly of complex mixtures of DNA at room or physiological temperature for generating user-defined programmable nanostructures capable of shape selection and transformation.

Rotaxanes are interlocked molecules that can undergo sliding and rotational movements and can be used in artificial molecular machines and motors. Here, Simmel and co-workers show a rigid rotaxane structures consisting of DNA origami subunits that can slide over several hundreds of nanometres.

Many synthetic DNA nanomachines have been developed and demonstratedin vitro, but their use in living organisms has not been reported. Now, a DNA nanomachine, the I-switch, is used to map spatiotemporal pH changes associated with endosomal maturation within coelomocytes of Caenorhabditis elegans.

DNA circuits hold promise for advancing information-based molecular technologies, yet it is challenging to design and construct them in practice. Thubagereet al. build DNA strand displacement circuits using unpurified strands whose sequences are automatically generated from a user-friendly compiler.

Controlling the threshold response in synthetic molecular structures is challenging. Here, the authors report on the buckling of ring-shaped DNA origami structures into twisted architectures via mechanical instability, induced by DNA intercalators.

DNA nanoswitch calipers can measure distances within single molecules with atomic resolution. Applied to single-molecule proteomics, they can enable the identification and quantification of molecules in trace samples via mechanical fingerprinting.

Strand displacement is commonly used in DNA nanotechnology to program dynamic interactions between individual DNA strands. Here, the authors describe a tile displacement principle that is similar in concept but occurs on a larger structural level: the displacement reactions take place between DNA origami tiles, allowing reconfiguration of entire systems of interacting DNA structures.