Self-assembly of DNA into nanoscale three-dimensional shapes

Molecular self-assembly offers a 'bottom-up' route to fabrication with subnanometre precision of complex structures from simple components(1). DNA has proved to be a versatile building block(2-5) for programmable construction of such objects, including two-dimensional crystals(6), nanotubes(7-11), and three-dimensional wire-frame nanopolyhedra(12-17). Templated self-assembly of DNA(18) into custom two-dimensional shapes on the megadalton scale has been demonstrated previously with a multiple-kilobase 'scaffold strand' that is folded into a flat array of antiparallel helices by interactions with hundreds of oligonucleotide 'staple strands'(19,20). Here we extend this method to building custom three-dimensional shapes formed as pleated layers of helices constrained to a honeycomb lattice. We demonstrate the design and assembly of nanostructures approximating six shapes-monolith, square nut, railed bridge, genie bottle, stacked cross, slotted cross-with precisely controlled dimensions ranging from 10 to 100 nm. We also show hierarchical assembly of structures such as homomultimeric linear tracks and heterotrimeric wireframe icosahedra. Proper assembly requires week-long folding times and calibrated monovalent and divalent cation concentrations. We anticipate that our strategy for self-assembling custom three-dimensional shapes will provide a general route to the manufacture of sophisticated devices bearing features on the nanometre scale.