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      Towards XNA nanotechnology: new materials from synthetic genetic polymers

      review-article
      * ,
      Trends in Biotechnology
      Elsevier Science Publishers

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          Highlights

          • We review recent advances in nucleic acid chemistry and polymerase engineering that have enabled the synthesis, replication, and evolution of a wide range of nucleic acid-like synthetic genetic polymers (XNAs) with improved chemical and biological stability.

          • We discuss the likely biotechnological impact of the further development of XNA technology for the generation of novel ligands, enzymes, and nanostructures with tailor-made chemistry.

          Abstract

          Nucleic acids display remarkable properties beyond information storage and propagation. The well-understood base pairing rules have enabled nucleic acids to be assembled into nanostructures of ever increasing complexity. Although nanostructures can be constructed using other building blocks, including peptides and lipids, it is the capacity to evolve that sets nucleic acids apart from all other nanoscale building materials. Nonetheless, the poor chemical and biological stability of DNA and RNA constrain their applications. Recent advances in nucleic acid chemistry and polymerase engineering enable the synthesis, replication, and evolution of a range of synthetic genetic polymers (XNAs) with improved chemical and biological stability. We discuss the impact of this technology on the generation of XNA ligands, enzymes, and nanostructures with tailor-made chemistry.

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          Most cited references107

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          A DNA-based method for rationally assembling nanoparticles into macroscopic materials.

          Colloidal particles of metals and semiconductors have potentially useful optical, optoelectronic and material properties that derive from their small (nanoscopic) size. These properties might lead to applications including chemical sensors, spectroscopic enhancers, quantum dot and nanostructure fabrication, and microimaging methods. A great deal of control can now be exercised over the chemical composition, size and polydispersity of colloidal particles, and many methods have been developed for assembling them into useful aggregates and materials. Here we describe a method for assembling colloidal gold nanoparticles rationally and reversibly into macroscopic aggregates. The method involves attaching to the surfaces of two batches of 13-nm gold particles non-complementary DNA oligonucleotides capped with thiol groups, which bind to gold. When we add to the solution an oligonucleotide duplex with 'sticky ends' that are complementary to the two grafted sequences, the nanoparticles self-assemble into aggregates. This assembly process can be reversed by thermal denaturation. This strategy should now make it possible to tailor the optical, electronic and structural properties of the colloidal aggregates by using the specificity of DNA interactions to direct the interactions between particles of different size and composition.
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            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 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.

              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.
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                Author and article information

                Contributors
                Journal
                Trends Biotechnol
                Trends Biotechnol
                Trends in Biotechnology
                Elsevier Science Publishers
                0167-7799
                1879-3096
                1 June 2014
                June 2014
                : 32
                : 6
                : 321-328
                Affiliations
                [0005]MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK
                Author notes
                [*]

                Current address: Institute of Structural and Molecular Biology, University College London, Darwin Building, Gower Street, London, WC1E 6BT, UK.

                Article
                S0167-7799(14)00063-8
                10.1016/j.tibtech.2014.03.010
                4039137
                24745974
                22f5c9a7-ccbc-4b1f-8fb0-898d7d4ca055
                © 2014 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).

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                Review

                Biotechnology
                Biotechnology

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