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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.

Self-assembly of DNA can provide access to a range of nanoscale structures, but assembly using magnesium has been considered essential. Martin and Dietz report conditions that allow the assembly of templated, multi-layer DNA structures in the presence of monovalent ions, rather than magnesium.

By using DNA sequence information to encode the shapes of DNA origami building blocks, shape-programmable assemblies can be created, with sizes and complexities similar to those of viruses.

All necessary strands for DNA origami can be created in a single scalable process by using bacteriophages to generate single-stranded precursor DNA containing the target sequences interleaved with self-excising DNA enzymes.

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.

An integrated experimental and deep learning pipeline reveals cell-level targeting of nanocarriers in whole bodies.

Precision design of DNA origami needs precision validation. Here, the authors developed cryo-EM methods for obtaining high resolution structural data and for constructing pseudo-atomic models in a semi-automated fashion, allowing for iterative nanodevice inspection and refinement.

Mauersberger and colleagues show that loss of function of soluble guanylyl cyclase (sGC) in platelets increases plaque burden in atherosclerosis-prone Ldlr^−/− mice by increasing leukocyte adhesion to atherosclerotic plaques. While mouse platelets lacking sGC and human platelets from carriers of GUCY1A1 risk alleles showed reduced secretion of angiopoietin-1, pharmacological sGC stimulation increased platelet angiopoietin-1 release in vitro and reduced leukocyte recruitment and atherosclerotic plaque formation in vivo, suggesting sGC as a potential therapeutic target for the treatment and prevention of atherosclerosis.

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.

Staufer et al. provide a protocol for preparation of synthetic minimal virions (MiniV) of SARS-CoV-2, mimicking viral structure and allowing for precise investigation of receptor binding mechanism. They find that the highly conserved free fatty acid binding pocket (FABP) can function as an allosteric regulator, enabling adaptation of immunogenicity via binding of proinflammatory free fatty acids and mediating the spike open to-closed equilibrium.

DNA origami may enable more versatile gene delivery applications through its ability to create custom nanoscale objects. Here the authors show that genes folded in DNA origami with custom scaffolds express efficiently when delivered to mammalian cells and can be assembled into multimeric arrays to deliver and express defined ratios of multiple genes simultaneously.

A self-assembled DNA structure is coupled to a nanopore and exhibits continuous rotation in the presence of nanoscale flows driven by electric fields or ionic gradients.

Synthetic DNA-labelled polymers can be made to self-assemble on two- and three-dimensional DNA scaffolds in custom routings.

Improved control over the shape of nanoparticles and the interactions between them allows the rational construction of intricate microscale assemblies.

DNA origami can be used to control the movement of nanoscale assemblies. Here the authors construct multiple-micrometer-long hollow DNA filaments through which DNA pistons move with micrometer-per-second speeds.

Programmable triangular DNA blocks self-assemble into distinct icosahedral shells with specific geometry and apertures that can encapsulate viruses and decrease viral infection.

Sequence-programmable self-assembly of DNA enables the formation of a variety of complex structures; however, determining the quality of these multi-chain structures is challenging. Here the authors address this problem by using a fluorescent probe to measure the amount of unpaired bases in the DNA assemblies.

A nanoscale rotary motor made of DNA origami, driven by ratcheting and powered by an external electric field, shows the ability to wind up a spring and has mechanical capabilities approaching those of biological motors.

Biological molecular motors convert chemical energy into mechanical motion by coupling catalytic reactions to large-scale structural transitions. Here, the authors report the design of a rotating DNA nanomechanism that comprises a camshaft whose rotary motion can be transformed into reciprocating large-scale transitions in the structure of the surrounding stator.

DNA has proved to be a versatile building block in the creation of complex structures through self-assembly, exploiting the intermolecular forces between the components. Here, the arrangement of DNA helices on pleated strands which are then assembled into honeycomb-like three-dimensional structures, produces objects of unprecedented complexity.

A molecular positioning device made from DNA origami can adjust the average distance between fluorescent molecules and reactive groups in steps as small as 0.04 nm.

FG-Nups are disordered proteins in the nuclear pore complex (NPC) where they selectively control nuclear transport. Here authors build NPC-mimics based on DNA origami rings which attach a certain numbers of Nups to analyse those nanopores by cryoEM and conductance measurements.

Recent advancements in DNA nanotechnology are enabling the construction of both aesthetically pleasing and functional structures using synthetic DNA strands, paving the way for practical applications in various fields.

Artificial DNA membrane channels are promising molecular devices for biotechnology but suffer from low affinity for lipid bilayers. Here, the authors report a large DNA nanopore that spontaneously inserts into a flat lipid membrane, driven by engineered hydrophobic or streptavidin-biotin interactions.

A trap, formed by a DNA-origami sphere docked onto a solid-state nanopore, allows the hydrodynamic trapping and label-free observation of single proteins, enabling nucleotide-dependent protein conformation to be discriminated on the timescale of submilliseconds to hours.

DNA origami allows the design of rod-shaped particles with specific geometrical features. This is exploited to examine how particle-level characteristics affect properties of the bulk phase and the superstructures such colloids assemble into.

The Yersinia YaxAB system is a pore-forming toxin of so far unknown structure. Here authors present X-ray and cryo-EM to structures of individual subunits and of the YaxAB pore complex, and find that YaxA binds to membranes first and recruits YaxB for subsequent oligomerization.

BAR domain proteins feature a “banana-like” shape which is thought to aid membrane scaffolding and membrane tubulation. Here authors use DNA origami mimicking BAR domains, giant unilamellar vesicles and fluorescence imaging to study how different BAR domain shapes bind and deform membranes.

This Review discusses the potential of DNA for creating machines that are both encoded by and built from DNA molecules. Alongside an overview of DNA nanostructure assembly, the authors describe recent advances and the remaining challenges, highlighting applications of custom DNA nanostructures as scientific tools.