DNA nanotechnology

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DNA nanotechnology involves the creation of artificial, designed nanostructures out of nucleic acids, such as this DNA tetrahedron.[1] Each edge of the tetrahedron is a 20 base pair DNA double helix, and each vertex is a three-arm junction.

DNA nanotechnology is a branch of nanotechnology that specializes in the design and manufacture of artificial nucleic acid structures for technological uses. The same properties that make nucleic acids useful as the carrier of genetic information in living cells serve it well as an non-biological engineering material: due to the specific base pairing rules of nucleic acids, only portions of nucleic acid strands with complementary base sequences bind together to form strong, rigid nucleic acid double helix molecules. This property allows for rational design of base sequences so that a set of strands will assemble to form a desired target structure, leading to a unique ability to form designed, complex structures with precise control over nanoscale features. DNA is the dominant material used, but structures incorporating other nucleic acids such as RNA and peptide nucleic acid (PNA) have also been constructed, leading to occasional use of the alternate name nucleic acid nanotechnology to describe the field.

The conceptual foundation for DNA nanotechnology was first laid out by Nadrian Seeman in the early 1980s, and the field began to attract widespread interest in the early to mid 2000s. Researchers in the field have created both static structures such as two- and three-dimensional crystal lattices, nanotubes, polyhedra, and arbitrary shapes made by the DNA origami method; and functional structures such as molecular machines and DNA computers. The field is beginning to be used as a tool to solve basic science problems in structural biology and biophysics, including applications in crystallography and spectroscopy for protein structure determination. Potential real-world applications in molecular scale electronics and nanomedicine are also being investigated.

Contents

[edit] Fundamental concepts

These four strands associate into a DNA four-arm junction because this structure maximizes the number of correct base pairs, with A matched to T and C matched to G.[2] See this image for a more realistic model of the four-arm junction showing its tertiary structure.
This double-crossover (DX) molecule consists of five DNA single strands that form two double-helical domains, on the left and the right in this image. There are two crossover points where the strands cross from one domain into the other.[2]

The goal of nanotechnology is to construct materials and devices with features on a scale less than 100 nanometers. DNA nanotechnology is an example of the molecular self-assembly approach to nanotechnology, where pre-existing molecular components spontaneously form a larger, organized structure due to their physical and chemical properties.[3] Nucleic acids such as DNA are well-suited to nanoscale construction, as a nucleic acid double helix has a diameter of 2 nm and a helical repeat length of 3.5 nm. The key property which makes nucleic acids more useful for constructing structures than other materials is that the binding between two nucleic acid strands depends on simple base pairing rules which are well understood, and form a specific structure upon binding, making the assembly of nucleic acid structures easy to control through nucleic acid design. This property is absent in other materials used in nanotechnology, including proteins, for which protein design is very difficult, and nanoparticles, which lack the capability for specific assembly on their own.[4]

The structure of a nucleic acid molecule consists of a sequence of nucleotides, distinguished by which nucleobase they contain. In DNA, the four bases present are adenine (A), cytosine (C), guanine (G), and thymine (T). Nucleic acids have the property that two molecules will bind to each other to form a double helix only if the two sequences are complementary, meaning that they form matching sequences of base pairs, with A only binding to T, and C only to G.[4][5] Because the formation of correctly matched base pairs is energetically favorable, nucleic acid strands are expected in most cases to bind to each other in the conformation that maximizes the number of correctly paired bases. The sequences of bases in a system of strands thus determine the pattern of binding and the overall structure in an easily controllable way. In DNA nanotechnology, the base sequences of strands are rationally designed by researchers so that the base pairing interactions cause the strands to assemble in the desired conformation.[4][6]

DNA nanotechnology is sometimes divided into two overlapping subfields: structural DNA nanotechnology and dynamic DNA nanotechnology. Structural DNA nanotechnology, sometimes abbreviated as SDN, focuses on synthesizing and characterizing nucleic acid complexes and materials which assemble into a static, equilibrium end state. On the other hand, dynamic DNA nanotechnology focuses on complexes with useful non-equilibrium behavior such as the ability to reconfigure based on a chemical or physical stimulus. Some complexes combine features of both the structural and dynamic subfields, such as nucleic acid nanomechanical devices.[7][8]

The complexes constructed in structural DNA nanotechnology make use of branched nucleic acid structures containing junctions, unlike most biological DNA, which exists as an unbranched double helix. One of the simplest branched structures, and the first made, is a four-arm junction that consists of four individual DNA strands, portions of which are complementary in a specific pattern. Unlike in natural Holliday junctions, each arm in the artificial immobile four-arm junction has a different base sequence, causing the junction point to be fixed at a certain position. Multiple junctions can also be combined in the same molecule; the most widely used of these is the "double-crossover" (DX) motif. A DX molecule can be imagined as containing two parallel double helical domains, where individual strands cross from one domain into the other at two crossover points. Each crossover point is itself topologically a four-arm junction, but ones which are constrained to a single orientation, as opposed to the flexible single four-arm junction. This rigidity makes the DX motif suitable as a structural building block for larger DNA complexes.[4][6]

Dynamic DNA nanotechnology often uses a mechanism called toehold-mediated strand displacement to allow the nucleic acid complexes to reconfigure. In this reaction, a strand binds to a single-stranded toehold region of a double-stranded complex, and then displaces one of the strands bound in the original complex through a branch migration process. The overall effect is that one of the strands in the complex is replaced with another one, which allows the presence of the first strand to act as a switch to control the reconfiguration of the complex.[7] In addition, reconfigurable structures and devices can be made using functional nucleic acids such as deoxyribozymes and ribozymes, which are capable of performing chemical reactions, and aptamers, which can bind to specific proteins or small molecules.[9]

[edit] Design

DNA nanostructures must be rationally designed so that the individual nucleic acid strands will assemble into the desired structures. This process usually begins with the specification of a desired target structure or functionality. Then, the overall secondary structure of the target molecule is determined, specifying the arrangement of nucleic acid strands within the structure, and which portions of those strands should be bound to each other. The last step is the primary structure design, which is the specification of the actual base sequences of each nucleic acid strand.[10][11]

[edit] Structural design

The first step in designing a nucleic acid nanostructure is to decide how a given structure should be represented by a specific arrangement of nucleic acid strands. This design step determines the secondary structure, or the series of base pairs that hold the individual strands together in the desired shape.[10] Several approaches have been demonstrated:

  • Tile-based structures. This approach breaks the target structure into smaller units with strong binding between the strands contained in each unit, and weaker interactions between the units. It is often used to make periodic lattices, but can also be used to implement algorithmic self-assembly, making them one platform for DNA computing. This was the dominant design strategy used from the mid 1990s until the mid 2000s, when the DNA origami methodology was developed.[10][12]
  • Folding structures. An alternative to the tile-based approach, folding approaches make the nanostructure out of a single long strand. This long strand can either have a designed sequence that folds due to its interactions with itself, or it can be folded into the desired shape by using shorter, "staple" strands. This latter method is called DNA origami, which allows the creation of nanoscale two- and three-dimensional shapes (see Arbitrary shapes below).[13][14]
  • Dynamic assembly. This approach directly controls the kinetics of DNA self-assembly, specifying not only the fully formed product of the assembly reaction, but also all the intermediate steps in the reaction mechanism. This is done using a nucleic acid hairpin structure as the starting material, which assembles in a cascade reaction in a specific order. This class of methods has the advantage of proceeding isothermally, and thus does not involve the thermal annealing step that is required by solely thermodynamic approaches.[13][15]

[edit] Sequence design

Main article: Nucleic acid design

After any of the above approaches are used to design the secondary structure of a target molecule, an actual sequence of nucleotides must be devised that will form into the desired structure. Nucleic acid design is the process of assigning a specific nucleic acid base sequence to each strand so that they will associate into a desired conformation. Most methods have the goal of designing sequences so that the target structure have the lowest energy, and is thus the most thermodynamically favorable, and misassembled structures have higher energies and are thus disfavored. This is done either through heuristic methods such as sequence symmetry minimization, or by explicitly using a full nearest-neighbor thermodynamic model. Geometric models are used to examine tertiary structure of the nanostructures and ensure that the complexes are not overly strained.[11][16]

Nucleic acid design has similar goals to protein design: in both, the sequence of monomers is designed to favor the desired folded or associated structure and to disfavor alternate structures. Nucleic acid design has the advantage of being much computationally simpler than protein design, since the simplicity of Watson-Crick base pairing rules leads to simple heuristic methods that yield experimentally robust designs. However, nucleic acid structures are less versatile than proteins in their functionality.[16]

[edit] Structural DNA nanotechnology

Structural DNA nanotechnology, sometimes abbreviated as SDN, focuses on synthesizing and characterizing nucleic acid complexes and materials with various nanoscale structures. Structural DNA nanotechnology is largely based on the fact that the three-dimensional structure of DNA—the nucleic acid double helix— has a robust, defined geometry that makes it possible to predict and design the structures of more complex DNA molecules. Many such structures have been created, including two- and three-dimensional structures; and periodic, aperiodic, and discrete structures.[8]

[edit] Extended lattices

The assembly of a DX array. Left, schematic diagram. Each bar represents a double-helical domain of DNA, with the shapes representing complimentary sticky ends. The DX molecule at top will combine with other DX molecules into the two-dimensional array shown at bottom.[2] Right, an atomic force microscope image of the assembled array. The individual DX tiles are clearly visible within the assembled structure. The field is 150 nm across.
Left, a model of a DNA tile used to make another two-dimensional periodic lattice. Right, an atomic force micrograph of the assembled lattice.[17]
An example of an aperiodic two-dimensional lattice that assembles into a fractal pattern. Left, the Sierpinski gasket fractal. Right, DNA arrays that display a representation of the Sierpinski gasket on their surfaces[18]

Small nucleic acid complexes can be equipped with sticky ends in order to combine them into a larger two-dimensional periodic lattices containing a specific tessellated pattern of the individual molecular tiles.[8] The earliest example of this used DX, or double-crossover, molecules as the basic tiles, each containing four sticky ends designed with sequences that caused the DX units to combine into periodic two-dimensional flat sheets that are essentially rigid two-dimensional crystals of DNA.[19][20] Two-dimensional arrays have been made out of other motifs as well, including the Holliday junction rhombus lattice[21] as well as various DX-based arrays making use of a double-cohesion scheme.[22][23]

Two-dimensional arrays can also be made to exhibit aperiodic structures whose assembly implements a specific algorithm, making them one form of DNA computing.[24] The DX tiles can have their sticky end sequences chosen so that they act as Wang tiles, allowing them to perform computation. A DX array has been demonstrated whose assembly encodes an XOR operation; this allows the DNA array to implement a cellular automaton that generates a fractal called the Sierpinski gasket.[18] Another system has the function of a binary counter, displaying a representation of increasing binary numbers as it grows. These results show that computation can be incorporated into the assembly of DNA arrays, increasing its scope beyond simple periodic arrays.[25]

DX arrays have been made to form hollow 4–20 nm-diameter nanotubes, which are essentially two-dimensional lattices which curve back upon themselves.[10] These DNA nanotubes are somewhat similar in size and shape to carbon nanotubes, and while they lack the electrical conduction ability of carbon nanotubes, DNA nanotubes are more easily modified and connected to other structures. There have been multiple schemes for constructing DNA nanotubes, one of which uses the inherent curvature of DX tiles to form a DX lattice to curl around itself and close into a tube.[26] An alternative design uses single-stranded tiles for which the rigidity of the tube is an emergent property. This method has the benefit of being able to specify the circumference of the nanotube in a simple, modular fashion.[27]

Creating three-dimensional lattices out of DNA was the earliest goal of DNA nanotechnology, but proved to be one of the most difficult to realize. Success in constructing three-dimensional DNA lattices was finally reported in 2009 using a motif based on the concept of tensegrity, a balance between tension and compression forces.[24][28]

[edit] Discrete structures

Researchers have synthesized a number of three-dimensional DNA molecules that each have the connectivity of a polyhedron such as a cube or octahedron, meaning that the DNA duplexes trace the edges of a polyhedron with a DNA junction at each vertex.[13] The earliest demonstrations of DNA polyhedra were vary work-intensive, requiring multiple ligations and solid-phase synthesis steps to create catenated polyhedra.[29] Subsequent work yielded polyhedra whose synthesis was much easier. These include a DNA octahedron made from a long single strand designed to fold into the correct conformation,[30] as well as a tetrahedron that can be produced from four DNA strands in a single step, pictured at the top of this article.[1]

Nanostructures of arbitrary, non-regular shapes are usually made using the DNA origami method. DNA origami makes use of a long natural virus strand as a "scaffold" strand, and computationally designs shorter "staple" strands that bind to portions of the scaffold strand and force it to fold into the desired shape. This method has the advantage of being easy to design, as the base sequence is predetermined by the scaffold strand sequence. It also does not require high strand purity and accurate stoichiometry, as most other DNA nanotechnology methods do. DNA origami was first demonstrated for two-dimensional shapes; demonstrated designs included the smiley face and a coarse map of North America.[13][14]

DNA origami was later extended to solid three-dimensional shapes.[13] One method creates solid shapes by filling the desired space with parallel DNA helices arranged in a honeycomb pattern.[31] Another approach uses structures with two-dimensional faces which fold into an overall three-dimensional shape, akin to a cardboard box. These can be programmed to open and release their cargo in response to a stimulus, making them potentially useful as programmable molecular cages.[32][33]

[edit] Templated assembly

The incorporation of molecules other than nucleic acids into these structures allows materials and devices to be made with a range of functionalities much greater than is possible with nucleic acids alone. The main idea is that self-assembly of the DNA structures templated the assembly of the nanoparticles hosted on them.[13] The schemes used include covalently attaching gold nanoparticles to a DX-based tile,[34] arranging streptavidin protein molecules into the pattern of the letters "D" "N" and "A" on a 4×4 DX array,[35] for which a hierarchical assembly was demonstrated that scales to larger arrays (8×8 and 8.96 MD),[36] and a non-covalent hosting scheme using Dervan polyamides on a DX array to arrange streptavidin proteins on specific kinds of tiles on the DNA array.[37][38] There has also been interest in using DNA nanotechnology to assemble molecular electronics devices, such as for the assembly of single-wall carbon nanotubes into field-effect transistors.[39]

[edit] Dynamic DNA nanotechnology

DNA nanotechnology focuses on creating molecules with designed dynamic functionalities related to their overall structures, such as computation and mechanical motion. There is some overlap between structural and dynamic DNA nanotechnology, as structures can be formed through annealing but then be reconfigured dynamically, or can be made to form dynamically in the first place.[13][40]

[edit] Nanomechanical devices

Main article: DNA machine

DNA complexes have been made that change their conformation upon some stimulus, making them one form of nanorobotics. These structures are initially formed in the same way as the static structures made in structural DNA nanotechnology, but are designed so that dynamic reconfiguration is possible after the initial assembly.[7][40] The earliest such device made use of the transition between the B-DNA and Z-DNA forms to respond to a change in buffer conditions by undergoing a twisting motion.[41] This reliance on buffer conditions, however, caused all devices to change state at the same time. A subsequent system was demonstrated that changed from an open to a closed state based upon the presence of control strands, allowing multiple devices to be individually operated in solution.[42] This was followed up by another system that relies on the presence of control strands to switch from a paranemic-crossover (PX) conformation to a double-junction (JX2) conformation,[43] and a two-dimensional array that could dynamically expand and contract in response to control strands.[44] Structures have also been made which dynamically open and/or close, potentially acting as a molecular cage to release or reveal a functional cargo upon opening.[32][45][46]

Another type of nucleic acid nanomachines, called DNA walkers, exhibit directional motion along a linear track. A large number of schemes have been demonstrated.[40] One strategy is to control the motion of the walker along the track using control strands that need to be manually added in sequence.[47][48] Another approach is to make use of restriction enzymes or deoxyribozymes to cleave the strands and cause the walker to move forward, which has the advantage of running autonomously.[49][50] A later system extended the concept of DNA walkers to walk upon a two-dimensional surface rather than a linear track, and demonstrated the ability to selectively pick up and move molecular cargo.[51] Additionally, a linear walker has been demonstrated that performs DNA-templated synthesis as the walker advances along the track, allowing autonomous multistep chemical synthesis directed by the walker.[52]

[edit] Strand displacement cascades

Because strand displacement reactions can be designed to free or reveal a new sequence as its output, the reactions can be linked to each other into a cascade linking several such reactions. The goal of this could be either to make dynamically assembled structures,[15] or for non-structural uses such as logic gates and reaction networks.[53] These cascades are made energetically favorable through the formation of new base pairs and/or the entropy gain resulting from disassembly reactions. The properties of nucleic acids allow reaction networks to be made which have more components and have more complex computational and information processing ability than other methods, and also allows for catalytic functionality of the initiator species.[7]

[edit] Applications

DNA nanotechnology provides one of the only ways to form designed, complex structures with precise control over nanoscale features. The field is beginning to see application to solve basic science problems in structural biology and biophysics. One such application, the earliest envisaged for the field, is in crystallography, where molecules that are hard to crystallize by themselves could be arranged and oriented within a three-dimensional nucleic acid lattice, thus allowing determination of their structure. DNA origami rods have also been used to replace liquid crystals in residual dipolar coupling experiments in protein NMR spectroscopy; using DNA origami is advantageous because, unlike liquid crystals, they are tolerant of the detergents needed to suspend membrane proteins in solution. It has been demonstrated that DNA walkers can be used as nanoscale assembly lines to move nanoparticles and direct chemical synthesis. Furthermore, DNA origami structures have aided in the biophysical studies of enzyme function and protein folding.[8][54]

DNA nanotechnology is also moving towards potential real-world applications. It has been suggested that the ability of nucleic acid arrays to arrange other molecules has potential applications in molecular scale electronics, with the assembly of a nucleic acid lattice templating the assembly of molecular electronic elements such as molecular wires.[8] It has been suggested that nucleic acid nanostructures could provide a method for nanometer-scale control of the placement and overall architecture of these components, essentially using nucleic acid structures as a molecular breadboard.[13] DNA nanotechnology has been called a form of programmable matter because of the coupling of computation to its material properties.[55]

There are potential applications for DNA nanotechnology in nanomedicine, making use of its ability to perform computation in a biocompatible format to make "smart drugs" for targeted drug delivery. One such system being investigated uses a hollow DNA box containing proteins that induce apoptosis, or cell death, that will only open when in proximity to a cancer cell.[54][56] There has additionally been interest in expressing these artificial structures in engineered living bacterial cells, most likely using the transcribed RNA for the assembly, although it is unknown whether these complex structures are able to efficiently fold or assemble in the cell's cytoplasm. If successful, this could enable directed evolution of nucleic acid nanostructures.[13]

[edit] Materials and methods

The sequences of the individual DNA strands that make up the target structure are designed computationally, using molecular modeling and thermodynamic modeling software.[11][16] Once the sequences have been designed, the nucleic acid molecules themselves are synthesized through standard oligonucleotide synthesis methods. This process is usually automated by using a machine called an oligonucleotide synthesizer, and nucleic acids of custom sequence are commercially available from many vendors.[57] For methods that require pure strands of known concentration, the nucleic acid strands can be purified using denaturing gel electrophoresis,[58] and concentrations are determined by one of several nucleic acid quantitation methods using ultraviolet absorbance spectroscopy.[59]

The fully formed target structures are usually characterized by native gel electrophoresis, which provides information about the size and shape of DNA molecules. An electrophoretic mobility shift assay can indicate whether a structure incorporates all the individual desired strands.[60] Fluorescent labeling and Förster resonance energy transfer (FRET) are sometimes used to characterize the structure of the molecules.[61]

Nucleic acid structures can be directly imaged by atomic force microscopy, which is well suited to extended two-dimensional structures, but is less useful for discrete three-dimensional structures due to the interaction of the microscope tip with the fragile nucleic acid structure. For these latter structures transmission electron microscopy and cryo-electron microscopy are important methods. Extended three-dimensional lattices are analyzed by X-ray crystallography.[62][63]

[edit] History

The woodcut Depth (pictured) by M. C. Escher reportedly inspired Nadrian Seeman to consider using three-dimensional lattices of DNA to orient hard-to-crystallize molecules. This led to the beginning of the field of DNA nanotechnology.

The conceptual foundation for DNA nanotechnology was first laid out by Nadrian Seeman in the early 1980s.[64] Seeman's original motivation was to create a three-dimensional DNA lattice for orienting other large molecules, which would simplify their crystallographic study by eliminating the difficult process of obtaining pure crystals. This idea had reportedly come to him in late 1980, after realizing the similarity between the woodcut Depth by M. C. Escher and an array of DNA six-arm junctions.[6][65] A number of natural branched DNA molecules were known at the time, including the DNA replication fork and the mobile Holliday junction, but Seeman's insight was that immobile nucleic acid junctions could be created by properly designing the strand sequences to remove symmetry in the assembled molecule, and that these immoble junctions could in principle be combined into rigid crystalline lattices. The first theoretical paper proposing this scheme was published in 1982, and the first experimental demonstration of an immoble DNA junction was published the following year.[13][4]

Seeman's laboratory in 1991 published the synthesis of a cube made of DNA, the first synthetic three-dimensional nucleic acid nanostructure, for which he received the 1995 Feynman Prize in Nanotechnology, which was followed by a DNA truncated octahedron. However, it soon became clear that these molecules, polygonal shapes with flexible junctions as their vertices, were not rigid enough to form extended three-dimensional lattices. Seeman developed the more rigid double-crossover (DX) motif, and in collaboration with Erik Winfree, in 1998 published the creation of two-dimensional lattices of DX tiles.[6][64][66] These tile-based structures had the advantage that they provided the capability to implement DNA computing, which was demonstrated by Winfree and Paul Rothemund in their 2004 paper on the algorithmic self-assembly of a Sierpinski gasket structure, and for which they shared the 2006 Feynman Prize in Nanotechnology. Winfree's key insight was that the DX tiles could be used as Wang tiles, meaning that their assembly was capable of performing computation.[64] The synthesis of a three-dimensional lattice was finally published by Seeman in 2009, nearly thirty years after he had set out to do so.[54]

New capabilities continued to be discovered for designed DNA structures throughout the 2000s. The first DNA nanomachine—a motif that changes its structure in response to an input—was demonstrated in 1999 by Seeman. An improved system was demonstrated by Bernard Yurke the following year, which was the first nucleic acid device to make use of toehold-mediated strand displacement. The next advance was to translate this into mechanical motion, and in 2004 and 2005, a number of DNA walker systems were demonstrated by the groups of Nadrian Seeman, Niles Pierce, Andrew Turberfield, and Chengde Mao.[40] The idea of using DNA arrays to template the assembly of other molecules such as nanoparticles and proteins, first suggested by Bruche Robinson and Seeman in 1987,[67] was demonstrated in 2006 and 2007 by the groups of Hao Yan, Peter Dervan, and Thomas LaBean.[4][37]

In 2006, Rothemund first demonstrated the new DNA origami technique for easily and robustly creating folded DNA molecules of any shape. Rothemund had conceived of this method as being conceptually intermediate between Seeman's DX lattices, which used many short strands, and William Shih's DNA octahedron, which consisted mostly of one very long strand; Rothemund's DNA origami contains a long strand whose folding is assisted by a number of short strands. This method allowed the creation of much larger structures than were previously possible, and which are less technically demanding to design and synthesize.[66] DNA origami was the cover story of Nature on March 15, 2006.[14] Rothemund's research demonstrating two-dimensional DNA origami structures was followed by the demonstration of solid three-dimensional DNA origami by Douglas et al. in 2009,[31] while the labs of Jørgen Kjems and Yan demonstrated hollow three-dimensional structures made out of two-dimensional faces.[54]

DNA nanotechnology as a field was initially met with some skepticism due to the unusual non-biological use of nucleic acids as a material for building structures and doing computation, as well as the preponderance of proof of principle experiments that extended the capabilities of the field but were far from actual applications. Seeman's seminal 1991 paper on the synthesis of the DNA cube was rejected by the journal Science after one reviewer praised its originality while another criticized it for its lack of biological relevance. By the early 2010s, however, the field was considered to have increased its capabilities to the point that applications for basic science research were beginning to be realized, and practical applications in medicine and other fields were beginning to be considered feasible.[54][68] The field had grown from very few active laboratories in 2001, to at least 60 in 2010, which increased the talent pool and thus the number of scientific advances in the field during that decade.[24]

[edit] See also

[edit] References

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  9. ^ Dynamic DNA nanotechnology: Lu, Yi; Liu, Juewen (December 2006). "Functional DNA nanotechnology: Emerging applications of DNAzymes and aptamers". Current Opinion in Biotechnology 17 (6): 580–588. doi:10.1016/j.copbio.2006.10.004. PMID 17056247.  edit
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  13. ^ a b c d e f g h i j Overview: Pinheiro, Andre V.; Han, Dongran; Shih, William M.; Yan, Hao (December 2011). "Challenges and opportunities for structural DNA nanotechnology". Nature Nanotechnology 6 (12): 763–772. doi:10.1038/nnano.2011.187. PMID 22056726.  edit
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  21. ^ Other arrays: Mao, Chengde; Sun, Weiqiong; Seeman, Nadrian C. (16 June 1999). "Designed two-dimensional DNA Holliday junction arrays visualized by atomic force microscopy". Journal of the American Chemical Society 121 (23): 5437–5443. doi:10.1021/ja9900398. 
  22. ^ Other arrays: Constantinou, Pamela E.; Wang, Tong; Kopatsch, Jens; Israel, Lisa B.; Zhang, Xiaoping; Ding, Baoquan; Sherman, William B.; Wang, Xing; Zheng, Jianping; Sha, Ruojie; Seeman, Nadrian C. (21 September 2006). "Double cohesion in structural DNA nanotechnology". Organic and Biomolecular Chemistry 4 (18): 3414–3419. doi:10.1039/b605212f. PMID 17036134. 
  23. ^ Other arrays: Mathieu, Frederick; Liao, Shiping; Kopatsch, Jens; Wang, Tong; Mao, Chengde; Seeman, Nadrian C. (April 2005). "Six-helix bundles designed from DNA". Nano Letters 5 (4): 661–665. Bibcode 2005NanoL...5..661M. doi:10.1021/nl050084f. PMID 15826105. 
  24. ^ a b c History: Seeman, Nadrian (9 June 2010). "Structural DNA nanotechnology: growing along with Nano Letters". Nano Letters 10 (6): 1971–1978. Bibcode 2010NanoL..10.1971S. doi:10.1021/nl101262u. PMC 2901229. PMID 20486672. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2901229. 
  25. ^ Algorithmic self-assembly: Barish, Robert D.; Rothemund, Paul W. K.; Winfree, Erik (December 2005). "Two computational primitives for algorithmic self-assembly: copying and counting". Nano Letters 5 (12): 2586–2592. Bibcode 2005NanoL...5.2586B. doi:10.1021/nl052038l. PMID 16351220. 
  26. ^ DNA nanotubes: Rothemund, Paul W. K.; Ekani-Nkodo, Axel; Papadakis, Nick; Kumar, Ashish; Fygenson, Deborah Kuchnir & Winfree, Erik (22 December 2004). "Design and Characterization of Programmable DNA Nanotubes". Journal of the American Chemical Society 126 (50): 16344–16352. doi:10.1021/ja044319l. PMID 15600335. 
  27. ^ DNA nanotubes: Yin, P.; Hariadi, R. F.; Sahu, S.; Choi, H. M. T.; Park, S. H.; Labean, T. H.; Reif, J. H. (8 August 2008). "Programming DNA Tube Circumferences". Science 321 (5890): 824–826. Bibcode 2008Sci...321..824Y. doi:10.1126/science.1157312. PMID 18687961. 
  28. ^ Three-dimensional arrays: Zheng, Jianping; Birktoft, Jens J.; Chen, Yi; Wang, Tong; Sha, Ruojie; Constantinou, Pamela E.; Ginell, Stephan L.; Mao, Chengde; Seeman, Nadrian C. (3 September 2009). "From molecular to macroscopic via the rational design of a self-assembled 3D DNA crystal". Nature 461 (7260): 74–77. Bibcode 2009Natur.461...74Z. doi:10.1038/nature08274. PMC 2764300. PMID 19727196. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2764300. 
  29. ^ DNA polyhedra: Zhang, Yuwen; Seeman, Nadrian C. (1 March 1994). "Construction of a DNA-truncated octahedron". Journal of the American Chemical Society 116 (5): 1661–1669. doi:10.1021/ja00084a006. 
  30. ^ DNA polyhedra: Shih, William M.; Quispe, Joel D.; Joyce, Gerald F. (12 February 2004). "A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron". Nature 427 (6975): 618–621. doi:10.1038/nature02307. PMID 14961116. 
  31. ^ a b DNA origami: Douglas, Shawn M.; Dietz, Hendrik; Liedl, Tim; Högberg, Björn; Graf, Franziska; Shih, William M. (21 May 2009). "Self-assembly of DNA into nanoscale three-dimensional shapes". Nature 459 (7245): 414–418. Bibcode 2009Natur.459..414D. doi:10.1038/nature08016. PMC 2688462. PMID 19458720. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2688462. 
  32. ^ a b DNA boxes: Andersen, Ebbe S.; Dong, Mingdong; Nielsen, Morten M.; Jahn, Kasper; Subramani, Ramesh; Mamdouh, Wael; Golas, Monika M.; Sander, Bjoern; Stark, Holger (7 May 2009). "Self-assembly of a nanoscale DNA box with a controllable lid". Nature 459 (7243): 73–76. Bibcode 2009Natur.459...73A. doi:10.1038/nature07971. PMID 19424153. 
  33. ^ DNA boxes: Ke, Yonggang; Sharma, Jaswinder; Liu, Minghui; Jahn, Kasper; Liu, Yan; Yan, Hao (10 June 2009). "Scaffolded DNA origami of a DNA tetrahedron molecular container". Nano Letters 9 (6): 2445–2447. Bibcode 2009NanoL...9.2445K. doi:10.1021/nl901165f. PMID 19419184. 
  34. ^ Nanoarchitecture: Zheng, Jiwen; Constantinou, Pamela E.; Micheel, Christine; Alivisatos, A. Paul; Kiehl, Richard A.; Seeman Nadrian C. (July 2006). "2D Nanoparticle Arrays Show the Organizational Power of Robust DNA Motifs". Nano Letters 6 (7): 1502–1504. Bibcode 2006NanoL...6.1502Z. doi:10.1021/nl060994c. PMID 16834438. 
  35. ^ Nanoarchitecture: Park, Sung Ha; Pistol, Constantin; Ahn, Sang Jung; Reif, John H.; Lebeck, Alvin R.; Dwyer, Chris; LaBean, Thomas H. (October 2006). "Finite-size, fully addressable DNA tile lattices formed by hierarchical assembly procedures". Angewandte Chemie 118 (40): 749–753. doi:10.1002/ange.200690141. 
  36. ^ Nanoarchitecture: Pistol, Constantin; Dwyer, Chris (March 2007). "Scalable, low-cost, hierarchical assembly of programmable DNA nanostructures". Nanotechnology 18 (12): 125305–9. Bibcode 2007Nanot..18l5305P. doi:10.1088/0957-4484/18/12/125305. 
  37. ^ a b Overview: Endo, Masayuki; Sugiyama, Hiroshi (12 October 2009). "Chemical approaches to DNA nanotechnology". ChemBioChem 10 (15): 2420–2443. doi:10.1002/cbic.200900286. PMID 19714700.  edit
  38. ^ Nanoarchitecture: Cohen, Justin D.; Sadowski, John P.; Dervan, Peter B. (22 October 2007). "Addressing single molecules on DNA nanostructures". Angewandte Chemie International Edition 46 (42): 7956–7959. doi:10.1002/anie.200702767. PMID 17763481. 
  39. ^ Nanoarchitecture: Maune, Hareem T.; Han, Si-Ping; Barish, Robert D.; Bockrath, Marc; Iii, William A. Goddard; Rothemund, Paul W. K.; Winfree, Erik (January 2009). "Self-assembly of carbon nanotubes into two-dimensional geometries using DNA origami templates". Nature Nanotechnology 5 (1): 61–66. Bibcode 2010NatNa...5...61M. doi:10.1038/nnano.2009.311. PMID 19898497. 
  40. ^ a b c d DNA machines: Bath, Jonathan; Turberfield, Andrew J. (May 2007). "DNA nanomachines". Nature Nanotechnology 2 (5): 275–284. Bibcode 2007NatNa...2..275B. doi:10.1038/nnano.2007.104. PMID 18654284. 
  41. ^ DNA machines: Mao, Chengde; Sun, Weiqiong; Shen, Zhiyong; Seeman, Nadrian C. (14 January 1999). "A DNA nanomechanical device based on the B-Z transition". Nature 397 (6715): 144–146. Bibcode 1999Natur.397..144M. doi:10.1038/16437. PMID 9923675. 
  42. ^ DNA machines: Yurke, Bernard; Turberfield, Andrew J.; Mills, Allen P., Jr; Simmel, Friedrich C.; Neumann, Jennifer L. (10 August 2000). "A DNA-fuelled molecular machine made of DNA". Nature 406 (6796): 605–609. Bibcode 2000Natur.406..605Y. doi:10.1038/35020524. PMID 10949296. 
  43. ^ DNA machines: Yan, Hao; Zhang, Xiaoping; Shen, Zhiyong; Seeman, Nadrian C. (3 January 2002). "A robust DNA mechanical device controlled by hybridization topology". Nature 415 (6867): 62–65. Bibcode 2002Natur.415...62Y. doi:10.1038/415062a. PMID 11780115. 
  44. ^ DNA machines: Feng, Liping; Park, Sung Ha; Reif, John H.; Yan, Hao (22 September 2003). "A two-state DNA lattice switched by DNA nanoactuator". Angewandte Chemie 115 (36): 4478. doi:10.1002/ange.200351818.  edit
  45. ^ DNA machines: Goodman, Russell P.; Heilemann, Mike; Doose, Sören; Erben, Cristoph M.; Kapanidis, Achillefs N.; Turberfield, Andrew J. (February 2008). "Reconfigurable, braced, three-dimensional DNA nanostructures". Nature Nanotechnology 3 (2): 93–96. doi:10.1038/nnano.2008.3. PMID 18654468.  edit
  46. ^ Applications: Douglas, Shawn M.; Bachelet, Ido; Church, George M. (17 February 2012). "A logic-gated nanorobot for targeted transport of molecular payloads". Science 335 (6070): 831. doi:10.1126/science.1214081.  edit
  47. ^ DNA walkers: Shin, Jong-Shik; Pierce, Niles A. (8 September 2004). "A synthetic DNA walker for molecular transport". Journal of the American Chemical Society 126 (35): 10834–10835. doi:10.1021/ja047543j. PMID 15339155. 
  48. ^ DNA walkers: Sherman, William B.; Seeman, Nadrian C. (July 2004). "A precisely controlled DNA biped walking device". Nano Letters 4 (7): 1203–1207. Bibcode 2004NanoL...4.1203S. doi:10.1021/nl049527q. 
  49. ^ DNA walkers: Tian, Ye; He, Yu; Chen, Yi; Yin, Peng; Mao, Chengde (11 July 2005). "A DNAzyme that walks processively and autonomously along a one-dimensional track". Angewandte Chemie 117 (28): 4429–4432. doi:10.1002/ange.200500703. 
  50. ^ DNA walkers: Bath, Jonathan; Green, Simon J.; Turberfield, Andrew J. (11 July 2005). "A free-running DNA motor powered by a nicking enzyme". Angewandte Chemie International Edition 44 (28): 4358–4361. doi:10.1002/anie.200501262. 
  51. ^ Functional DNA walkers: Lund, Kyle; Manzo, Anthony J.; Dabby, Nadine; Michelotti, Nicole; Johnson-Buck, Alexander; Nangreave, Jeanette; Taylor, Steven; Pei, Renjun; Stojanovic, Milan N. (13 May 2010). "Molecular robots guided by prescriptive landscapes". Nature 465 (7295): 206–210. Bibcode 2010Natur.465..206L. doi:10.1038/nature09012. PMC 2907518. PMID 20463735. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2907518. 
  52. ^ Functional DNA walkers: He, Yu; Liu, David R. (November 2010). "Autonomous multistep organic synthesis in a single isothermal solution mediated by a DNA walker". Nature Nanotechnology 5 (11): 778–782. Bibcode 2010NatNa...5..778H. doi:10.1038/nnano.2010.190. PMC 2974042. PMID 20935654. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2974042. 
  53. ^ Strand displacement cascades: Seelig, G.; Soloveichik, D.; Zhang, D. Y.; Winfree, E. (2006). "Enzyme-Free Nucleic Acid Logic Circuits". Science 314 (5805): 1585–1588. doi:10.1126/science.1132493. PMID 17158324.  edit
  54. ^ a b c d e History/applications: Service, Robert F. (3 June 2011). "DNA nanotechnology grows up". Science 332 (6034): 1140–1143. doi:10.1126/science.332.6034.1140. 
  55. ^ Applications: Rietman, Edward A. (2001). Molecular engineering of nanosystems. Springer. pp. 209–212. ISBN 978-0-387-98988-4. http://books.google.com/books?id=ga2DKYCm7xMC&pg=PA209. Retrieved 17 April 2011. 
  56. ^ Applications: Jungmann, Ralf; Renner, Stephan; Simmel, Friedrich C. (March 2008). "From DNA nanotechnology to synthetic biology". HFSP journal 2 (2): 99–109. doi:10.2976/1.2896331. PMC 2645571. PMID 19404476. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2645571. 
  57. ^ Methods: Ellington, Andrew; Pollard, Jr., Jack D. (1 May 2001). "Synthesis and purification of oligonucleotides". Current Protocols in Molecular Biology. doi:10.1002/0471142727.mb0211s42. ISBN 0471142727.  edit
  58. ^ Methods: Ellington, Andrew; Pollard, Jr., Jack D. (1 May 2001). "Purification of oligonucleotides using denaturing polyacrylamide gel electrophoresis". Current Protocols in Molecular Biology. doi:10.1002/0471142727.mb0212s42. ISBN 0471142727.  edit
  59. ^ Methods: Gallagher, Sean R.; Desjardins, Philippe (1 July 2011). "Quantitation of nucleic acids and proteins". Current Protocols Essential Laboratory Techniques. doi:10.1002/9780470089941.et0202s5. ISBN 0470089938.  edit
  60. ^ Methods: Chory, Joanne; Pollard, Jr., Jack D. (1 May 2001). "Separation of small DNA fragments by conventional gel electrophoresis". Current Protocols in Molecular Biology. doi:10.1002/0471142727.mb0207s47. ISBN 0471142727.  edit
  61. ^ Methods: Walter, Nils G. (1 February 2003). "Probing RNA structural dynamics and function by fluorescence resonance energy transfer (FRET)". Current Protocols in Nucleic Acid Chemistry. doi:10.1002/0471142700.nc1110s11. ISBN 0471142700.  edit
  62. ^ Methods: Lin, C.; Ke, Y.; Chhabra, R.; Sharma, J.; Liu, Y.; Yan, H. (2011). "Synthesis and Characterization of Self-Assembled DNA Nanostructures". In Zuccheri, G. and Samorì, B. DNA Nanotechnology: Methods and Protocols. Methods in Molecular Biology. 749. pp. 1–11. doi:10.1007/978-1-61779-142-0_1. ISBN 978-1-61779-141-3.  edit
  63. ^ Methods: Bloomfield, Victor A.; Crothers, Donald M., Tinoco, Jr., Ignacio (2000). Nucleic acids: structures, properties, and functions. Sausalito, Calif: University Science Books. pp. 84–86, 396–407. ISBN 0935702490. 
  64. ^ a b c History: Pelesko, John A. (2007). Self-assembly: the science of things that put themselves together. New York: Chapman & Hall/CRC. pp. 201, 242, 259. ISBN 978 1 58488 687 7. 
  65. ^ History: See "Current crystallization protocol". Nadrian Seeman Lab. http://seemanlab4.chem.nyu.edu/nano-pro.html.  for a statement of the problem, and "DNA cages containing oriented guests". Nadiran Seeman Laboratory. http://seemanlab4.chem.nyu.edu/nano-cage.html.  for the proposed solution.
  66. ^ a b DNA origami: Rothemund, Paul W. K. (2006). "Scaffolded DNA origami: from generalized multicrossovers to polygonal networks". In Chen, Junghuei; Jonoska, Natasha; Rozenberg, Grzegorz. Nanotechnology: science and computation. Natural Computing Series. New York: Springer. pp. 3–21. doi:10.1007/3-540-30296-4_1. ISBN 978 3 540 30295 7. 
  67. ^ Nanoarchitecture: Robinson, Bruche H.; Seeman, Nadrian C. (August 1987). "The design of a biochip: a self-assembling molecular-scale memory device". Protein Engineering 1 (4): 295–300. doi:10.1093/protein/1.4.295. PMID 3508280. 
  68. ^ History: Hopkin, Karen (August 2011). "Profile: 3-D seer". The Scientist. http://the-scientist.com/2011/08/01/3-d-seer/. Retrieved 8 August 2011. 

[edit] Further reading

  • Feldkamp, Udo; Niemeyer, Christof M. (13 March 2006). "Rational design of DNA nanoarchitectures". Angewandte Chemie International Edition 45 (12): 1856–76. doi:10.1002/anie.200502358. PMID 16470892. —A review coming from the viewpoint of secondary structure design
  • Lin, Chenxiang; Liu, Yan; Rinker, Sherri; Yan, Hao (11 August 2006). "DNA tile based self-assembly: building complex nanoarchitectures". ChemPhysChem 7 (8): 1641–1647. doi:10.1002/cphc.200600260. PMID 16832805. —A minireview specifically focusing on tile-based assembly
  • Zhang, David Yu; Seelig, Georg (February 2011). "Dynamic DNA nanotechnology using strand-displacement reactions". Nature Chemistry 3 (2): 103–113. Bibcode 2011NatCh...3..103Z. doi:10.1038/nchem.957. PMID 21258382. —A review of DNA systems making use of strand displacement mechanisms

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