DNA molecules have been used to build a variety of nanoscale structures and devices over the past 30 years, and potential applications have begun to emerge. But the development of more advanced structures and applications will require a number of issues to be addressed, the most significant of which are the high cost of DNA and the high error rate of self-assembly. Here we examine the technical challenges in the field of structural DNA nanotechnology and outline some of the promising applications that could be developed if these hurdles can be overcome. In particular, we highlight the potential use of DNA nanostructures in molecular and cellular biophysics, as biomimetic systems, in energy transfer and photonics, and in diagnostics and therapeutics for human health.
We present a strategy to design and construct self-assembling DNA nanostructures that define intricate curved surfaces in three-dimensional (3D) space using the DNA origami folding technique. Double-helical DNA is bent to follow the rounded contours of the target object, and potential strand crossovers are subsequently identified. Concentric rings of DNA are used to generate in-plane curvature, constrained to 2D by rationally designed geometries and crossover networks. Out-of-plane curvature is introduced by adjusting the particular position and pattern of crossovers between adjacent DNA double helices, whose conformation often deviates from the natural, B-form twist density. A series of DNA nanostructures with high curvature--such as 2D arrangements of concentric rings and 3D spherical shells, ellipsoidal shells, and a nanoflask--were assembled.
Topology is the mathematical study of the spatial properties that are preserved through the deformation, twisting and stretching of objects. Topological architectures are common in nature and can be seen, for example, in DNA molecules that condense and relax during cellular events 1 . Synthetic topological nanostructures, such as catenanes and rotaxanes, have been engineered using supramolecular chemistry, but the fabrication of complex and reconfigurable structures remains challenging 2 . Here, we show that DNA origami 3 can be used to assemble a Möbius strip, a topological ribbon-like structure that has only one side [4][5][6] . In addition, we show that the DNA Möbius strip can be reconfigured through strand displacement 7 to create topological objects such as supercoiled ring and catenane structures. This DNA fold-and-cut strategy, analogous to Japanese kirigami 8 , may be used to create and reconfigure programmable topological structures that are unprecedented in molecular engineering.Structural DNA nanotechnology 9 , which makes use of DNA as an information-coding polymer capable of programming nano-structure assembly, has proven its utility in creating sophisticated nanoscale geometrical objects [10][11][12][13][14][15][16] . The recent development of DNA origami 3 , a method that uses short DNA oligos as staples to fold single-stranded genomic DNA scaffolds into geometrically defined two-( ref.3 ) and three-dimensional nanoarchitectures [17][18][19][20][21] , has opened up great opportunities for directed assembly of chemical and biomolecular species with exquisite positional control [22][23][24][25][26] .Engineering topologically complex molecular architectures represents an appealing challenge for chemists and materials scientists, because structures such as catenanes, rotaxanes and knots often display unique material properties 2 . Topological structures have been successfully generated through organic and supramolecular synthesis 27,28 . Earlier works from Seeman and colleagues have exploited enzymatic ligation of simple, branched DNA junctions to create configurations such as various knots 29 and a Borromean ring structure 30 , which were predicated on the relationships between topological crossing points and half-turns within B-DNA or Z-DNA. However, progress using DNA to achieve Here, we demonstrate a DNA origami technique that can be used to create sub-100-nm topological architectures that are reconfigurable. We chose the Möbius strip as our demonstration target, not only because it is artistically inspiring, but also because it will likely display unique material properties 4,5 that may be applied to create novel molecular devices 6 . The Möbius strip has several interesting characteristics. Topologically speaking, it is a surface with only one side and only one boundary. A model can be easily created by taking a paper strip and giving it a half-twist, and then joining the ends of the strip together to form a loop. Cutting along the centre line of the loop destroys a Möbius strip, yieldi...
Self-folding of an information-carrying polymer into a defined structure is foundational to biology and offers attractive potential as a synthetic strategy. Although multicomponent self-assembly has produced complex synthetic nanostructures, unimolecular folding has seen limited progress. We describe a framework to design and synthesize a single DNA or RNA strand to self-fold into a complex yet unknotted structure that approximates an arbitrary user-prescribed shape. We experimentally construct diverse multikilobase single-stranded structures, including a ~10,000-nucleotide (nt) DNA structure and a ~6000-nt RNA structure. We demonstrate facile replication of the strand in vitro and in living cells. The work here thus establishes unimolecular folding as a general strategy for constructing complex and replicable nucleic acid nanostructures, and expands the design space and material scalability for bottom-up nanotechnology.
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