ABSTRACT
6. Perspectives
5.4 Regulation of Enzyme Cascade Reactions
In living systems, a series of enzymatic reactions in a cascade way is conducted to mediate biological functions. The effi ciency and specifi city of enzyme cascade reactions rely on the appropriate spatial arrangement.
DNA nanotechnology provides predictable and programmable design of positioning nanoparticles in a precise manner. By taking advantage of this, previous studies have shown that it is feasible to locate multiple enzymes on static DNA nanostructures (Barrow et al. 2012). However, the distance between enzymes is determined and fi xed by the underlying DNA structures therefore, in order to mimic the enzyme cascade reaction in vitro where the location of enzymes is not consistent, scientists turned to dynamic DNA nanostructures (Xin et al. 2013, Liu et al. 2013). Following the work of using DNA tweezers to regulate protein binding, the similar design is used to attach two enzymes of glucose oxidase (GOx) and horse-radish peroxidase (HRP) to both arm ends of DNA tweezers (Fig. 8b). As the reaction occurs, GOx fi rst catalyzes oxidization of glucose to generate gluconic acid and H2O2, which is as the substrate of HRP and reduced into H2O. The turnover rate of GOx is much slower than HRP, therefore, the diffusion distance of H2O2 determines the rate of this enzyme cascade reaction. By deliberately tuning the state of DNA tweezers in closed and open state, the distance of GOx and HRP can be adjusted from several nanometers to about eighteen nanometers. In the closed state, GOx and HRP are brought into proximity, leading to a much closer diffusion pathway for H2O2. In contrast, in the open state, both enzymes are spatially separated, thus lowering enzymatic effi ciency. It is shown that several cycles of regulation of enzyme cascade reaction are successfully conducted. Furthermore, this proof-of-concept is also confi rmed in another system to actuate the activity of an enzyme/
cofactor pair. A dehydrogenase and NAD+ cofactor are fi xed on DNA tweezers, and the enzyme inhibition and activation is reversibly turned on and off upon tuning the open and closed state of DNA tweezers, respectively. This approach opens up the design of dynamically regulating other enzyme systems and mimicking enzyme cascade reaction outside of living organisms.
growth in research interest. Compared with Seeman’s early works in the last century, people are now able to build complex 2D and 3D artifi cial DNA nanostructures with defi ned geometry, look into its inherent physical, mechanical, electrical and biological properties, assemble higher-order and larger patterns, and narrow the gap between top-down and bottom- up. Applications of DNA-based smart materials are also a fast-growing research fi eld.
Looking towards the future, the current research on DNA-based materials is still in its early stages and more challenges remain to be solved.
First, for DNA-nanoparticles conjugates, though various methods of combining DNA and nanoparticles have been established, there is still a big challenge to develop new conjugation strategies in order to realize spatially controlled and anisotropic conjugation on nanoparticles. In addition, further improvement to the methods of conjugating DNA with biological components, which usually contain multiple functional groups on the surface, and how to connect DNA to specifi c site without changing its biological functions need to be addressed.
Second, for static DNA nanostructures including polyhedrons and origami, there are more questions that are waiting for answers.
Fundamentally, we are still not clear about the formation mechanism of many DNA nanostructures, especially DNA origami, and need to improve the yield, quality and stability, simplify the preparation, and make it cheaper. From the structural point of view, it is constantly expected to build more complex, larger and stronger structures with controlled addressability and fl exibility that could be manipulated by present scientifi c instruments. In terms of future applications, several aspects are foreseen for further investigation. One is artifi cial bio-nanoreactor: it is expected that DNA-biomolecule conjugates anchored on spatially addressable DNA template to form controlled cascades, which could mimic in vivo bioreactions in compartments. Addressable nanocircuits, based on self-assembled DNA-meal nanoparticle patterns, should also be studied to overcome the limits of optical lithography. Furthermore, nanophotonic devices, also DNA-metal nanoparticles assembled on DNA 2D/3D templates to form metal nanoparticle arrays with controlled plasmonic modes, are promising devices. More efforts should also be devoted to developing structures from nano to micro even macro scale, and use DNA-nanoparticle conjugates as artifi cial atoms for the construction of fi nite or infi nite, periodic or aperiodic large structures.
Third, for DNA nanomachines, we here consider that the following issues might be the most important challenges for future development.
Experimental and theoretical studies on the single DNA nanomachine should be carried out to understand its energy conversion mechanism and entropy exchange with environment. New power supplying methods,
which could be easily incorporated into current silicon based nanodevices, should be developed. The reliability of DNA nanomachines and multi-component DNA nanomachines are also expected to be studied.
In addition, the construction of dynamic structures for incorporation of multiple nanoparticles and study of the complex, multiple interactions is needed. Most importantly, to continuously and precisely control the spatial distance in nanoscale by DNA nanomachines should be highlighted, which will provide a new platform of mimicking polyvalent interactions in vitro.
Finally, in the long term, the cost and quality of DNA is an issue.
So far, the DNA for constructing nanostructures and conjugating with nanoparticles is programmed and synthesized. Lowering the cost and synthesis on a large scale would promote the application of DNA-based materials. The quality of DNA structures, such as uniformity, stability and toxicity also need to be improved in future studies.
In summary, with the fast development of DNA-based smart materials for nanoconstructions, the awaited evolution process in this fi eld will be fascinating and we believe DNA will play a more important role in materials science in the coming decade.
References
Acuna, G .P., F.M. Moller, P. Holzmeister, S. Beater, B. Lalkens and P. Tinnefeld. 2012. Fluorescence enhancement at docking sites of DNA-directed self-assembled nanoantennas. Science 338: 506–510.
Agapakis , C.M., P.M. Boyle and P.A. Silver. 2012. Natural strategies for the spatial optimization of metabolism in synthetic biology. Nat. Chem. Biol. 8: 527–535.
Aghebat Rafat, A., T. Pirzer, M.B. Scheible, A. Kostina and F.C. Simmel. 2014. Surface-assisted large-scale ordering of DNA origami tiles. Angew. Chem. Int. Ed. 53: 7665–7668.
Aldaye, F.A. and H.F. Sleiman. 2007. Modular access to structurally switchable 3D discrete DNA assemblies. J. Am. Chem. Soc. 129: 13376–13377.
Andersen , E.S., M. Dong, M.M. Nielsen, K. Jahn, A. Lind-Thomsen, W. Mamdouh, K.V. Gothelf, F. Besenbacher and J. Kjems. 2008a. DNA origami design of dolphin-shaped structures with fl exible tails. ACS Nano 2: 1213–1218.
Andersen , E.S., M. Dong, M.M. Nielsen, K. Jahn, R. Subramani, W. Mamdouh, M.M. Golas, B. Sander, H. Stark, C.L. Oliveira, J.S. Pedersen, V. Birkedal, F. Besenbacher, K.V. Gothelf and J. Kjems. 2009. Self-assembly of a nanoscale DNA box with a controllable lid. Nature 459: 73–76.
Andersen , F.F., B. Knudsen, C.L. Oliveira, R.F. Frohlich, D. Kruger, J. Bungert, M. Agbandje- McKenna, R. McKenna, S. Juul, C. Veigaard, J. Koch, J.L. Rubinstein, B. Guldbrandtsen, M.S. Hede, G. Karlsson, A.H. Andersen, J.S. Pedersen and B.R. Knudsen. 2008b. Assembly and structural analysis of a covalently closed nano-scale DNA cage. Nucl. Acids Res.
36: 1113–1139.
Bagalkot , V., O.C. Farokhzad, R. Langer and S. Jon. 2006. An aptamer-doxorubicin physical conjugate as a novel targeted drug-delivery platform. Angew. Chem. Int. Ed.
45: 8149–8152.
Barrow, S.J., X. Wei, J.S. Baldauf, A.M. Funston and P. Mulvaney. 2012. The surface plasmon modes of self-assembled gold nanocrystals. Nat. Commun. 3: 1275.
Bellot, G., M.A. McClintock, C. Lin and W.M. Shih. 2011. Recovery of intact DNA nanostructures after agarose gel-based separation. Nat. Methods 8: 192–194.
Bu, N.N. , A. Gao, X.W. He and X.B. Yin. 2013. Electrochemiluminescent biosensor of ATP using tetrahedron structured DNA and a functional oligonucleotide for Ru(phen)3(2+) intercalation and target identifi cation. Biosens Bioelectron. 43: 200–204.
Bu, N.N. , C.X. Tang, X.W. He and X.B. Yin. 2011. Tetrahedron-structured DNA and functional oligonucleotide for construction of an electrochemical DNA-based biosensor. Chem.
Commun. 47: 7689–7691.
Bui, H., C. Onodera, C. Kidwell, Y. Tan, E. Graugnard, W. Kuang, J. Lee, W.B. Knowlton, B. Yurke and W.L. Hughes. 2010. Programmable periodicity of quantum dot arrays with DNA origami nanotubes. Nano Lett. 10: 3367–3372.
Charoenp hol, P. and H. Bermudez. 2014. Aptamer-targeted DNA nanostructures for therapeutic delivery. Mol. Pharm. 11: 1721–1725.
Chen, A. H. and P.A. Silver. 2012. Designing biological compartmentalization. Trends Cell Biol. 22: 662–670.
Chen, J. H. and N.C. Seeman. 1991. Synthesis from DNA of a molecule with the connectivity of a cube. Nature 350: 631–633.
Chen, P. , Y. Sun, H. Liu, L. Xu, Q. Fan and D. Liu. 2010. A pH responsive dendron-DNA-protein hybrid supramolecular system. Soft Matter 6: 2143–2145.
Chen, Y. , S.-H. Lee and C. Mao. 2004. A DNA nanomachine based on a duplex–triplex transition.
Angew. Chem. Int. Ed. 43: 5335–5338.
Cheng, E ., Y. Xing, P. Chen, Y. Yang, Y. Sun, D. Zhou, L. Xu, Q. Fan and D. Liu. 2009. A pH- triggered, fast-responding DNA hydrogel. Angew. Chem. Int. Ed. 48: 7660–7663.
Choi, B. and G. Zocchi. 2006. Mimicking cAMP-dependent allosteric control of protein kinase a through mechanical tension. J. Am. Chem. Soc. 128: 8541–8548.
Dadova, J., P. Orsag, R. Pohl, M. Brazdova, M. Fojta and M. Hocek. 2013. Vinylsulfonamide and acrylamide modifi cation of DNA for crosslinking with proteins. Angew. Chem. Int.
Ed. 52: 10515–10518.
Dietz, H ., S.M. Douglas and W.M. Shih. 2009. Folding DNA into twisted and curved nanoscale shapes. Science 325: 725–730.
Ding, B. , Z. Deng, H. Yan, S. Cabrini, R.N. Zuckermann and J. Bokor. 2010. Gold nanoparticle self-similar chain structure organized by DNA origami. J. Am. Chem. Soc. 132: 3248–3249.
Douglas, S., H. Dietz, T. Liedl, B. Hogberg, F. Graf and W. Shih. 2009. Self-assembly of DNA into nanoscale three-dimensional shapes. Nature 459: 414–418.
Douglas, S.M., I. Bachelet and G.M. Church. 2012. A logic-gated nanorobot for targeted transport of molecular payloads. Science 335: 831–834.
Edwardso n, T.G.W., K.M.M. Carneiro, C.K. McLaughlin, C.J. Serpell and H.F. Sleiman. 2013.
Site-specifi c positioning of dendritic alkyl chains on DNA cages enables their geometry- dependent self-assembly. Nat. Chem. 5: 868–875.
Elbaz, J ., A. Cecconello, Z. Fan, A.O. Govorov and I. Willner. 2013. Powering the programmed nanostructure and function of gold nanoparticles with catenated DNA machines. Nat.
Commun. 4.
Endo, M. , T. Sugita, Y. Katsuda, K. Hidaka and H. Sugiyama. 2010. Programmed-assembly system using DNA jigsaw pieces. Chem. Eur. J. 16: 5362–5368.
Erben, C .M., R.P. Goodman and A.J. Turberfi eld. 2006. Single-molecule protein encapsulation in a rigid DNA cage. Angew. Chem. Int. Ed. 45: 7414–7417.
Erben, C .M., R.P. Goodman and A.J. Turberfi eld. 2007. A self-assembled DNA bipyramid. J.
Am. Chem. Soc. 129: 6992–6993.
Fahlman, R.P., M. Hsing, C.S. Sporer-Tuhten and D. Sen. 2003. Duplex pinching: a structural switch suitable for contractile DNA nanoconstructions. Nano Letters 3: 1073–1078.
Farlow, J., D. Seo, K.E. Broaders, M.J. Taylor, Z.J. Gartner and Y.-w. Jun. 2013. Formation of targeted monovalent quantum dots by steric exclusion. Nat. Methods 10: 1203–1205.
Fu, J., M. Liu, Y. Liu, N.W. Woodbury and H. Yan. 2012. Interenzyme substrate diffusion for an enzyme cascade organized on spatially addressable DNA nanostructures. J. Am.
Chem. Soc. 134: 5516–5519.
Fu, Y., D. Zeng, J. Chao, Y. Jin, Z. Zhang, H. Liu, D. Li, H. Ma, Q. Huang, K.V. Gothelf and C. Fan. 2013. Single-step rapid assembly of DNA origami nanostructures for addressable nanoscale bioreactors. J. Am. Chem. Soc. 135: 696–702.
Furman, J.L., A.H. Badran, O. Ajulo, J.R. Porter, C.I. Stains, D.J. Segal and I. Ghosh. 2010.
Toward a general approach for RNA-templated hierarchical assembly of split-proteins.
J. Am. Chem. Soc. 132: 11692–11701.
Ge, Z., H. Pei, L. Wang, S. Song and C. Fan. 2011. Electrochemical single nucleotide polymorphisms genotyping on surface immobilized three-dimensional branched DNA nanostructure. Sci. Chin. Chem. 54: 1273–1276.
Goodman, R.P., R.M. Berry and A.J. Turberfi eld. 2004. The single-step synthesis of a DNA tetrahedron. Chem. Commun.: 1372–1373.
Goodman, R.P., M. Heilemann, S. Doose, C.M. Erben, A.N. Kapanidis and A.J. Turberfi eld.
2008. Reconfi gurable, braced, three-dimensional DNA nanostructures. Nat. Nanotechnol.
3: 93–96.
Goodman, R.P., I.A. Schaap, C.F. Tardin, C.M. Erben, R.M. Berry, C.F. Schmidt and A.J. Turberfi eld. 2005. Rapid chiral assembly of rigid DNA building blocks for molecular nanofabrication. Science 310: 1661–1665.
Gramotne v, D.K. and S.I. Bozhevolnyi. 2010. Plasmonics beyond the diffraction limit. Nat.
Photonics 4: 83–91.
Gu, H., J. Chao, S.-J. Xiao and N.C. Seeman. 2010. A proximity-based programmable DNA nanoscale assembly line. Nature 465: 202–205.
Han, D., S. Pal, Y. Liu and H. Yan. 2010. Folding and cutting DNA into reconfi gurable topological nanostructures. Nat. Nanotechnol. 5: 712–717.
Han, D., S. Pal, J. Nangreave, Z. Deng, Y. Liu and H. Yan. 2011. DNA origami with complex curvatures in three-dimensional space. Science 332: 342–346.
Han, D.R ., S. Pal, Y. Yang, S.X. Jiang, J. Nangreave, Y. Liu and H. Yan. 2013. DNA gridiron nanostructures based on four-arm junctions. Science 339: 1412–1415.
He, Y. a nd C. Mao. 2006. Balancing fl exibility and stress in DNA nanostructures. Chem.
Commun.: 968–969.
He, Y., T. Ye, M. Su, C. Zhang, A.E. Ribbe, W. Jiang and C. Mao. 2008. Hierarchical self-assembly of DNA into symmetric supramolecular polyhedra. Nature 452: 198–201.
Hemmi, H ., O. Takeuchi, T. Kawai, T. Kaisho, S. Sato, H. Sanjo, M. Matsumoto, K. Hoshino, H. Wagner, K. Takeda and S. Akira. 2000. A Toll-like receptor recognizes bacterial DNA.
Nature 408: 740–745.
Hermanso n, G.T. 2008. Bioconjugate Techniques. 2nd ed. London: Academic Press.
Hogberg, B., T. Liedl and W.M. Shih. 2009. Folding DNA origami from a double-stranded source of scaffold. J. Am. Chem. Soc. 131: 9154–9155.
Ishizawa , T., T. Kawakami, P.C. Reid and H. Murakami. 2013. TRAP display: a high-speed selection method for the generation of functional polypeptides. J. Am. Chem. Soc.
135: 5433–5440.
Jiang, Q ., C. Song, J. Nangreave, X. Liu, L. Lin, D. Qiu, Z.G. Wang, G. Zou, X. Liang, H. Yan and B. Ding. 2012. DNA origami as a carrier for circumvention of drug resistance. J. Am.
Chem. Soc. 134: 13396–13403.
Jin, J., Y. Xing, Y. Xi, X. Liu, T. Zhou, X. Ma, Z. Yang, S. Wang and D. Liu. 2013. A triggered DNA hydrogel cover to envelop and release single cells. Adv. Mater. 25: 4714–4717.
Jones, M .R., N.C. Seeman and C.A. Mirkin. 2015. Nanomaterials. Programmable materials and the nature of the DNA bond. Science 347: 1260901.
Jungmann , R., T. Liedl, T.L. Sobey, W. Shih and F.C. Simmel. 2008. Isothermal assembly of DNA origami structures using denaturing agents. J. Am. Chem. Soc. 130: 10062–10063.
Kühler, P., E.-M. Roller, R. Schreiber, T. Liedl, T. Lohmüller and J. Feldmann. 2014. Plasmonic DNA-origami nanoantennas for surface-enhanced raman spectroscopy. Nano Letters 14: 2914–2919.
Ke, Y., S.M. Douglas, M. Liu, J. Sharma, A. Cheng, A. Leung, Y. Liu, W.M. Shih and H. Yan. 2009.
Multilayer DNA origami packed on a square lattice. J. Am. Chem. Soc. 131: 15903–15908.
Ke, Y.G. , L.L. Ong, W. Sun, J. Song, M.D. Dong, W.M. Shih and P. Yin. 2014. DNA brick crystals with prescribed depths. Nat. Chem. 6: 994–1002.
Kedracki , D., I. Safir, N. Gour, K.X. Ngo and C. Vebert-Nardin. 2013. DNA-polymer conjugates: from synthesis, through complex formation and self-assembly to applications.
In: Bio-Synthetic Polymer Conjugates, edited by H. Schlaad.
Kim, J.- W., J.-H. Kim and R. Deaton. 2011. DNA-linked nanoparticle building blocks for programmable matter. Angew. Chem. Int. Ed. 50: 9185–9190.
Klein, W .P., C.N. Schmidt, B. Rapp, S. Takabayashi, W.B. Knowlton, J. Lee, B. Yurke, W.L. Hughes, E. Graugnard and W. Kuang. 2013. Multiscaffold DNA origami nanoparticle waveguides. Nano Lett. 13: 3850–3856.
Ko, S.H. , G.M. Gallatin and J.A. Liddle. 2012. Nanomanufacturing with DNA origami: factors affecting the kinetics and yield of quantum dot binding. Adv. Funct. Mater. 22: 1015–1023.
Kuzuya, A., M. Kimura, K. Numajiri, N. Koshi, T. Ohnishi, F. Okada and M. Komiyama.
2009. Precisely programmed and robust 2D streptavidin nanoarrays by using periodical nanometer-scale wells embedded in DNA origami assembly. Chembiochem. 10: 1811–1815.
Kuzuya, A. and M. Komiyama. 2009. Design and construction of a box-shaped 3D-DNA origami. Chem. Commun.: 4182–4184.
Kuzyk, A ., K.T. Laitinen and P. Torma. 2009. DNA origami as a nanoscale template for protein assembly. Nanotechnology 20: 235305.
Kuzyk, A ., R. Schreiber, Z. Fan, G. Pardatscher, E.M. Roller, A. Hogele, F.C. Simmel, A.O. Govorov and T. Liedl. 2012. DNA-based self-assembly of chiral plasmonic nanostructures with tailored optical response. Nature 483: 311–314.
Kuzyk, A ., R. Schreiber, H. Zhang, A.O. Govorov, T. Liedl and N. Liu. 2014. Reconfi gurable 3D plasmonic metamolecules. Nat. Mater. 13: 862–866.
Kwak, M. and A. Herrmann. 2011. Nucleic acid amphiphiles: synthesis and self-assembled nanostructures. Chem. Soc. Rev. 40: 5745–5755.
Lan, X., Z. Chen, G. Dai, X. Lu, W. Ni and Q. Wang. 2013. Bifacial DNA origami-directed discrete, three-dimensional, anisotropic plasmonic nanoarchitectures with tailored optical chirality. J. Am. Chem. Soc. 135: 11441–11444.
Lapiene, V., F. Kukolka, K. Kiko, A. Arndt and C.M. Niemeyer. 2010. Conjugation of fl uorescent proteins with DNA oligonucleotides. Bioconjugate Chem. 21: 921–927.
Lee, H., W.C. DeLoache and J.E. Dueber. 2012a. Spatial organization of enzymes for metabolic engineering. Metab. Eng. 14: 242–251.
Lee, H., A.K. Lytton-Jean, Y. Chen, K.T. Love, A.I. Park, E.D. Karagiannis, A. Sehgal, W. Querbes, C.S. Zurenko, M. Jayaraman, C.G. Peng, K. Charisse, A. Borodovsky, M. Manoharan, J.S. Donahoe, J. Truelove, M. Nahrendorf, R. Langer and D.G. Anderson. 2012b.
Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery.
Nat. Nanotechnol. 7: 389–393.
Lee, J.B ., S. Peng, D. Yang, Y.H. Roh, H. Funabashi, N. Park, E.J. Rice, L. Chen, R. Long, M. Wu and D. Luo. 2012c. A mechanical metamaterial made from a DNA hydrogel. Nat.
Nanotechnol. 7: 816–820.
Leitner, M., N. Mitchell, M. Kastner, R. Schlapak, H.J. Gruber, P. Hinterdorfer, S. Howorka and A. Ebner. 2011. Single-molecule AFM characterization of individual chemically tagged DNA tetrahedra. ACS Nano 5: 7048–7054.
Li, J., H. Pei, B. Zhu, L. Liang, M. Wei, Y. He, N. Chen, D. Li, Q. Huang and C. Fan. 2011a.
Self-assembled multivalent DNA nanostructures for noninvasive intracellular delivery of immunostimulatory CpG oligonucleotides. ACS Nano 5: 8783–8789.
Li, J.J. and W. Tan. 2002. A single DNA molecule nanomotor. Nano Letters 2: 315–318.
Li, Z., E. Cheng, W. Huang, T. Zhang, Z. Yang, D. Liu and Z. Tang. 2011b. Improving the yield of Mono-DNA-Functionalized gold nanoparticles through dual steric hindrance. J. Am.
Chem. Soc. 133: 15284–15287.
Liu, D. and S. Balasubramanian. 2003. A proton-fuelled DNA nanomachine. Angew. Chem.
Int. Ed. 42: 5734–5736.
Liu, D., E. Cheng and Z. Yang. 2011. DNA-based switchable devices and materials. NPG Asia Mater. 3: 109–114.
Liu, H., T. Torring, M. Dong, C.B. Rosen, F. Besenbacher and K.V. Gothelf. 2010. DNA-templated covalent coupling of G4 PAMAM dendrimers. J. Am. Chem. Soc. 132: 18054–18056.
Liu, H., Y. Xu, F. Li, Y. Yang, W. Wang, Y. Song and D. Liu. 2007. Light-driven conformational switch of i-Motif DNA. Angew. Chem. Int. Ed. 46: 2515–2517.
Liu, M., J. Fu, C. Hejesen, Y. Yang, N.W. Woodbury, K. Gothelf, Y. Liu and H. Yan. 2013. A DNA tweezer-actuated enzyme nanoreactor. Nat. Commun. 4.
Liu, X., Y. Xu, T. Yu, C. Clifford, Y. Liu, H. Yan and Y. Chang. 2012. A DNA nanostructure platform for directed assembly of synthetic vaccines. Nano Lett. 12: 4254–4259.
Loweth, C.J., W.B. Caldwell, X. Peng, A.P. Alivisatos and P.G. Schultz. 1999. DNA-based assembly of gold nanocrystals. Angew. Chem. Int. Ed. 38: 1808–1812.
Lu, N., H. Pei, Z. Ge, C.R. Simmons, H. Yan and C. Fan. 2012. Charge transport within a three-dimensional DNA nanostructure framework. J. Am. Chem. Soc. 134: 13148–13151.
Lund, K. , A.J. Manzo, N. Dabby, N. Michelotti, A. Johnson-Buck, J. Nangreave, S. Taylor, R. Pei, M.N. Stojanovic, N.G. Walter, E. Winfree and H. Yan. 2010. Molecular robots guided by prescriptive landscapes. Nature 465: 206–210.
Mammen, M., S.-K. Choi and G.M. Whitesides. 1998. Polyvalent interactions in biological systems: implications for design and use of multivalent ligands and inhibitors. Angew.
Chem. Int. Ed. 37: 2754–2794.
Mao, C., W. Sun, Z. Shen and N.C. Seeman. 1999. A nanomechanical device based on the B-Z transition of DNA. Nature 397: 144–146.
Marchi, A.N., I. Saaem, B.N. Vogen, S. Brown and T.H. LaBean. 2014. Toward larger DNA origami. Nano Lett. 14: 5740–5747.
Martin, T.G. and H. Dietz. 2012. Magnesium-free self-assembly of multi-layer DNA objects.
Nat. Commun. 3: 1103.
Mashimo, Y., H. Maeda, M. Mie and E. Kobatake. 2012. Construction of semisynthetic DNA- protein conjugates with Phi X174 Gene-A* protein. Bioconjugate Chem. 23: 1349–1355.
Maune, H .T., S.P. Han, R.D. Barish, M. Bockrath, W.A. Iii, P.W. Rothemund and E. Winfree.
2010. Self-assembly of carbon nanotubes into two-dimensional geometries using DNA origami templates. Nat. Nanotechnol. 5: 61–66.
Meng, H. , Y. Yang, Y. Chen, Y. Zhou, Y. Liu, X.a. Chen, H. Ma, Z. Tang, D. Liu and L. Jiang.
2009. Photoelectric conversion switch based on quantum dots with i-motif DNA scaffolds.
Chem. Commun.: 2293–2295.
Mirkin, C.A., R.L. Letsinger, R.C. Mucic and J.J. Storhoff. 1996. A DNA-based method for rationally assembling nanoparticles into macroscopic materials. Nature 382: 607–609.
Miyoshi, D., H. Karimata, Z.-M. Wang, K. Koumoto and N. Sugimoto. 2007. Artifi cial G-Wire Switch with 2,2‘-Bipyridine units responsive to divalent metal ions. J. Am. Chem. Soc.
129: 5919–5925.
Monchaud , D., P. Yang, L. Lacroix, M.-P. Teulade-Fichou and J.-L. Mergny. 2008. A metal- mediated conformational switch controls G-quadruplex binding affi nity. Angew. Chem.
Int. Ed. 47: 4858–4861.
Nakata, E., F.F. Liew, C. Uwatoko, S. Kiyonaka, Y. Mori, Y. Katsuda, M. Endo, H. Sugiyama and T. Morii. 2012. Zinc-fi nger proteins for site-specifi c protein positioning on DNA-origami structures. Angew. Chem. Int. Ed. 51: 2421–2424.
Niemeyer , C.M. 2010. Semisynthetic DNA–Protein Conjugates for biosensing and nanofabrication. Angew. Chem. Int. Ed. 49: 1200–1216.
Ouyang, X., J. Li, H. Liu, B. Zhao, J. Yan, Y. Ma, S. Xiao, S. Song, Q. Huang, J. Chao and C. Fan.
2013. Rolling circle amplifi cation-based DNA origami nanostructrures for intracellular delivery of immunostimulatory drugs. Small 9: 3082–3087.
Pal, S., Z. Deng, B. Ding, H. Yan and Y. Liu. 2010. DNA-origami-directed self-assembly of discrete silver-nanoparticle architectures. Angew. Chem. Int. Ed. 49: 2700–2704.
Pal, S., Z. Deng, H. Wang, S. Zou, Y. Liu and H. Yan. 2011. DNA directed self-assembly of anisotropic plasmonic nanostructures. J. Am. Chem. Soc. 133: 17606–17609.
Pal, S., P. Dutta, H. Wang, Z. Deng, S. Zou, H. Yan and Y. Liu. 2013. Quantum effi ciency modifi cation of organic fl uorophores using gold nanoparticles on DNA origami scaffolds.
J. Phys. Chem. C 117: 12735–12744.
Park, N. , S.H. Um, H. Funabashi, J. Xu and D. Luo. 2009. A cell-free protein-producing gel.
Nat. Mater. 8: 432–437.
Pei, H., F. Li, Y. Wan, M. Wei, H. Liu, Y. Su, N. Chen, Q. Huang and C. Fan. 2012a. Designed diblock oligonucleotide for the synthesis of spatially isolated and highly hybridizable functionalization of DNA-gold nanoparticle nanoconjugates. J. Am. Chem. Soc.
134: 11876–11879.
Pei, H., L. Liang, G. Yao, J. Li, Q. Huang and C. Fan. 2012b. Reconfi gurable three-dimensional DNA nanostructures for the construction of intracellular logic sensors. Angew. Chem.
Int. Ed. 51: 9020–9024.
Pei, H., N. Lu, Y. Wen, S. Song, Y. Liu, H. Yan and C. Fan. 2010. A DNA nanostructure- based biomolecular probe carrier platform for electrochemical biosensing. Adv. Mater.
22: 4754–4758.
Pei, H., Y. Wan, J. Li, H. Hu, Y. Su, Q. Huang and C. Fan. 2011. Regenerable electrochemical immunological sensing at DNA nanostructure-decorated gold surfaces. Chem. Commun.
47: 6254–6256.
Pilo-Pai s, M., A. Watson, S. Demers, T.H. LaBean and G. Finkelstein. 2014. Surface-enhanced raman scattering plasmonic enhancement using DNA origami-based complex metallic nanostructures. Nano Letters 14: 2099–2104.
Qian, L. , Y. Wang, Z. Zhang, J. Zhao, D. Pan, Y. Zhang, Q. Liu, C. Fan, J. Hu and L. He. 2006.
Analogic China map constructed by DNA. Chin. Sci. Bull. 51: 2973–2976.
Röglin, L., M.R. Ahmadian and O. Seitz. 2007. DNA-controlled reversible switching of peptide conformation and bioactivity. Angew. Chem. Int. Ed. 46: 2704–2707.
Raindlov a, V., R. Pohl and M. Hocek. 2012. Synthesis of aldehyde-linked nucleotides and DNA and their bioconjugations with lysine and peptides through reductive amination.
Chem. Eur. J. 18: 4080–4087.
Rangneka r, A. and T.H. LaBean. 2014. Building DNA nanostructures for molecular computation, templated assembly, and biological applications. Acc. Chem. Res. 47: 1778–1788.
Rashidia n, M., J.K. Dozier and M.D. Distefano. 2013. Enzymatic labeling of proteins: techniques and approaches. Bioconjugate Chem. 24: 1277–1294.
Roh, Y.H ., R.C.H. Ruiz, S. Peng, J.B. Lee and D. Luo. 2011. Engineering DNA-based functional materials. Chem. Soc. Rev. 40: 5730–5744.
Rothemun d, P.W.K. 2006. Folding DNA to create nanoscale shapes and patterns. Nature 440:
297–302.
Rusling, D.A., A.R. Chandrasekaran, Y.P. Ohayon, T. Brown, K.R. Fox, R. Sha, C. Mao and N.C. Seeman. 2014. Functionalizing designer DNA crystals with a triple-helical veneer.
Angew. Chem. Int. Ed. 53: 3979–3982.
Rycenga, M., C.M. Cobley, J. Zeng, W. Li, C.H. Moran, Q. Zhang, D. Qin and Y. Xia. 2011.
Controlling the synthesis and assembly of silver nanostructures for plasmonic applications. Chem. Rev. 111: 3669–3712.
Saccà, B . and C.M. Niemeyer. 2012. DNA origami: the art of folding DNA. Angew. Chem.
Int. Ed. 51: 58–66.
Saccà, B ., R. Meyer, M. Erkelenz, K. Kiko, A. Arndt, H. Schroeder, K.S. Rabe and C.M. Niemeyer. 2010. Orthogonal protein decoration of DNA origami. Angew. Chem.
Int. Ed. 49: 9378–9383.