Self-Assembly of DNA into 3D Nanostructures Facilitated with caDNAno Tool
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Self-Assembly of DNA into 3D Nanostructures Facilitated with caDNAno Tool DNA has proven to be a versatile building block for the fabrication of nanostructures using bottom-up strategies. The design and self-assembly of DNA into twodimensional, megadalton structures have been demonstrated with a strategy that uses multiple-kilobase single strands of DNA that act as scaffolds, which fold into a flat array of antiparallel helices after interacting with hundreds of oligonucleotide strands conceptualized as staples. Recently, W.M. Shih and co-researchers from the Dana-Farber Cancer Institute, Harvard Medical School, and Harvard University have extended this method to the design and fabrication of three-dimensional (3D) nanostructures that are formed as pleated layers of helices constrained to a honeycomb lattice. Shih and co-researchers designed and assembled DNA nanostructures approximating a variety of shapes with precisely controlled dimensions ranging from 10 nm to 100 nm. Shih and co-researchers described their honeycomb pleat-based assembly strategy in a letter published in the May 21 issue of Nature (DOI: 10.1038/nature08016; p. 414). As shown in Figure 1, double helices consisting of scaffold strands and staple strands create an unfolded, two-dimensional form of the target shape. Helices that are depicted as adjacent in the conceptual folding intermediate presented in Figure 1 are connected by a mixture of staple and scaffold crossovers, while the helices that are adjacent in the final structure but not in the conceptual folding intermediate are connected only by staple crossovers (both staple and scaffold crossovers are phosphate linkages). The researchers likened the first step in the design process to sculpting a shape from a crystalline block; unwanted DNA helices are carved away from the honeycomb lattice of antiparallel helices. Next, scaffold crossovers at a subset of allowed positions are introduced to create a singular scaffold path that visits all remaining duplex segments. Staple crossovers are then added at posi-
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Figure 1. (a) An unrolled two-dimensional schematic of the target shape. Grey scaffold strands and orange, white, and blue staple strands form double helices that run parallel to the z-axis. Crossovers between adjacent helices are made with phosphate linkages, while stable crossovers (shown as semicircular arcs) bridge different layers. (b) Partial folding is illustrated with a conceptual intermediate model composed of cylinders. (c) A fully folded target shape, which also shows cross-sectional slices (i–iii) of parallel helices arranged in a honeycomb pattern in the x-y plane. (d) An atomistic model of
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