Gigadalton-scale shape-programmable DNA assemblies

TLDR: This method, which enables the self-assembly of structures with sizes approaching that of viruses and cellular organelles, can readily be used to create a range of other complex structures with well defined sizes, by exploiting the modularity and high degree of addressability of the DNA origami building blocks used.

Abstract: 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. In nature, large and complex structures such as viruses assemble with ease, but building such large and complex artificial objects remains a grand challenge. Hendrik Dietz and colleagues now show that large and discrete objects can be created efficiently by using DNA sequence information to encode the shapes of individual DNA origami building blocks, and the geometry and details of the interactions between these building blocks to control their copy numbers, positions and orientations within higher-order assemblies. The team create planar rings reaching 350 nanometres in diameter, tubes the size of some bacilli, and three-dimensional polyhedral cages 450 nanometres in diameter, which strikingly illustrate the capability of this method. The technique can in principle be adjusted to create other assemblies that might find use in drug delivery, as scaffolds or for creating complex machine-like objects. Three related papers is this issue report further advances in DNA origami, and all four are summarized in a News & Views. Natural biomolecular assemblies such as molecular motors, enzymes, viruses and subcellular structures often form by self-limiting hierarchical oligomerization of multiple subunits1,2,3. Large structures can also assemble efficiently from a few components by combining hierarchical assembly and symmetry, a strategy exemplified by viral capsids4. De novo protein design5,6,7,8,9 and RNA10,11 and DNA nanotechnology12,13,14 aim to mimic these capabilities, but the bottom-up construction of artificial structures with the dimensions and complexity of viruses and other subcellular components remains challenging. Here we show that natural assembly principles can be combined with the methods of DNA origami15,16,17,18,19,20,21,22,23,24 to produce gigadalton-scale structures with controlled sizes. DNA sequence information is used to encode the shapes of individual DNA origami building blocks, and the geometry and details of the interactions between these building blocks then control their copy numbers, positions and orientations within higher-order assemblies. We illustrate this strategy by creating planar rings of up to 350 nanometres in diameter and with atomic masses of up to 330 megadaltons, micrometre-long, thick tubes commensurate in size to some bacilli, and three-dimensional polyhedral assemblies with sizes of up to 1.2 gigadaltons and 450 nanometres in diameter. We achieve efficient assembly, with yields of up to 90 per cent, by using building blocks with validated structure and sufficient rigidity, and an accurate design with interaction motifs that ensure that hierarchical assembly is self-limiting and able to proceed in equilibrium to allow for error correction. We expect that our method, which enables the self-assembly of structures with sizes approaching that of viruses and cellular organelles, can readily be used to create a range of other complex structures with well defined sizes, by exploiting the modularity and high degree of addressability of the DNA origami building blocks used.