Building machines with DNA molecules

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Abstract

In Nature, DNA molecules carry the hereditary information. But DNA has physical and chemical properties that make it attractive for uses beyond heredity. In this Review, we discuss the potential of DNA for creating machines that are both encoded by and built from DNA molecules. We review the main methods of DNA nanostructure assembly, describe recent advances in building increasingly complex molecular structures, and discuss strategies for creating machine-like nanostructures that can be actuated and move. We highlight opportunities for applications of custom DNA nanostructures as scientific tools to address challenges across biology, chemistry and engineering.

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Self-assembly of DNA into nanoscale three-dimensional shapes

Shawn M. Douglas, Hendrik Dietz, Tim Liedl … (2009)

Molecular self-assembly offers a ‘bottom-up’ route to fabrication with subnanometre precision of complex structures from simple components1. DNA has proven a versatile building block2–5 for programmable construction of such objects, including two-dimensional crystals6, nanotubes7–11, and three-dimensional wireframe nanopolyhedra12–17. Templated self-assembly of DNA18 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 of 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 nanometer scale.

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A logic-gated nanorobot for targeted transport of molecular payloads.

Shawn M. Douglas, Ido Bachelet, George M. Church (2012)

We describe an autonomous DNA nanorobot capable of transporting molecular payloads to cells, sensing cell surface inputs for conditional, triggered activation, and reconfiguring its structure for payload delivery. The device can be loaded with a variety of materials in a highly organized fashion and is controlled by an aptamer-encoded logic gate, enabling it to respond to a wide array of cues. We implemented several different logical AND gates and demonstrate their efficacy in selective regulation of nanorobot function. As a proof of principle, nanorobots loaded with combinations of antibody fragments were used in two different types of cell-signaling stimulation in tissue culture. Our prototype could inspire new designs with different selectivities and biologically active payloads for cell-targeting tasks.