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Spherical nucleic acids (SNAs)〔Cutler, J. I., et al., Spherical Nucleic Acids. ''J Am Chem Soc'' 2012, 134 (3), 1376-1391.〕 – defined as structures which are an arrangement of densely packed, highly oriented nucleic acids in a spherical geometry – were first introduced in 1996〔Mirkin, C. A., et al., A DNA-based method for rationally assembling nanoparticles into macroscopic materials. ''Nature'' 1996, 382 (6592), 607-609.〕 by the Mirkin group at Northwestern University. The unique arrangement and orientation of one-dimensional linear nucleic acids within this three-dimensional framework results in fundamentally new chemical, biological, and physical properties, which represent a paradigm shift in the use of nucleic acids for intracellular gene regulation, molecular diagnostics, and materials synthesis applications. == Structure and Function == The first SNA consisted of 3’ alkanethiol-terminated, single-stranded oligonucleotides (short DNA sequences) covalently attached to the surface of spherical gold nanoparticles. A dense nucleic acid loading was achieved through a series of salt additions, in which positively charged counterions were used to reduce electrostatic repulsion between adjacent negatively charged DNA strands and thereby enable more efficient DNA packing onto the nanoparticle surface. One- and two-dimensional forms of nucleic acids (e.g., single strands, linear duplexes, and plasmids) are important biological machinery for the storage and transmission of genetic information (Fig. 1). Underlying this utility are the bioprogrammable interactions between complementary nucleotide bases. Scientists and engineers have been synthesizing and, in certain cases, mass-producing such structures for decades in an effort to understand and exploit this elegant recognition motif. The recognition abilities of nucleic acids are enhanced when arranged in a spherical geometry, which allows for polyvalent interactions. This polyvalency, along with the high density and degree of orientation described above, helps to explain why a three-dimensional nucleic acid structure fundamentally composed of linear, one-dimensional nucleic acids exhibits dramatically different properties than its lower-dimensional constituents (Fig. 2). Two decades of research on SNAs have revealed that they exhibit a synergistic combination of properties resulting from the inorganic core and the nucleic acid shell. The inorganic nanoparticle core (in addition to gold, silver,〔Lee, J. S., et al., Silver nanoparticle-oligonucleotide conjugates based on DNA with triple cyclic disulfide moieties. ''Nano Lett'' 2007, 7 (7), 2112-2115.〕 iron oxide,〔Cutler, J. I., et al., Polyvalent Oligonucleotide Iron Oxide Nanoparticle "Click" Conjugates. ''Nano Lett'' 2010, 10 (4), 1477-1480.〕 silica,〔Xue, C., et al., Self-assembled monolayer mediated silica coating of silver triangular nanoprisms. ''Adv Mater'' 2007, 19 (22), 4071.〕 and semiconductor materials〔Mitchell, G. P., et al., Programmed assembly of DNA functionalized quantum dots. ''J Am Chem Soc'' 1999, 121 (35), 8122-8123.〕 have also been used) serves two purposes: 1) it imparts upon the conjugate novel physical and chemical properties (e.g. plasmonic, catalytic,〔〔Taton, T. A., et al., Scanometric DNA array detection with nanoparticle probes. Science 2000, 289 (5485), 1757-1760.〕 magnetic,〔 luminescent〔), and 2) it acts as a scaffold for the assembly and orientation of nucleic acids into the dense arrangement that gives rise to many of their functional properties. The nucleic acid shell gives the conjugate unique, programmable chemical and biological recognition abilities that offer greater binding strengths and higher duplex stabilities compared to the same sequence of linear DNA,〔Cutler, J. I., et al., Polyvalent Nucleic Acid Nanostructures. ''J Am Chem Soc'' 2011, 133 (24), 9254-9257.〕〔Prigodich, A. E., et al., Tailoring DNA Structure To Increase Target Hybridization Kinetics on Surfaces. ''J Am Chem Soc'' 2010, 132 (31), 10638-10641.〕〔Rosi, N. L., et al., Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. ''Science'' 2006, 312 (5776), 1027-1030.〕 cooperative melting behavior with DNA strands of a complementary sequence, and enhanced cellular uptake without the use of transfection agents.〔Lytton-Jean, A. K. R.; Mirkin, C. A., A thermodynamic investigation into the binding properties of DNA functionalized gold nanoparticle probes and molecular fluorophore probes. ''J Am Chem Soc'' 2005, 127 (37), 12754-12755.〕 Recent studies have shown that one can crosslink the DNA strands at their base, and subsequently dissolve the inorganic core with KCN or I2 to create a new coreless form of SNA (Fig. 3, right),〔Hurst, S. J., et al., "Three-Dimensional Hybridization" with polyvalent DNA-gold nanoparticle conjugates. ''J Am Chem Soc'' 2008, 130 (36), 12192-12200.〕 which exhibits many of the hallmark properties of the original DNA-nanoparticle conjugate (Fig. 3, left). This work underscores one of the fundamental features of SNAs: the properties of these nanomaterials are core-independent, derived from the orientation and packing of the nucleic acid shell. Due to their unique structure and function, SNAs occupy a materials space distinct from “DNA nanotechnology and origami.”〔Han, D. R., et al., DNA Origami with Complex Curvatures in Three-Dimensional Space. ''Science'' 2011, 332 (6027), 342-346.〕〔Seeman, N. C., DNA in a material world. ''Nature'' 2003, 421 (6921), 427-431.〕〔Seeman, N. C., An overview of structural DNA Nanotechnology. ''Mol Biotechnol'' 2007, 37 (3), 246-257.〕 With DNA origami, such structures are synthesized via DNA hybridization events. In contrast, the SNA structure can be synthesized independent of nucleic acid sequence and hybridization, instead relying upon robust chemical bond formation between nanoparticles and nucleic acid adsorbates. Furthermore, DNA origami uses DNA hybridization interactions to realize a final structure, whereas SNAs and other forms of three-dimensional nucleic acids (structures templated with a triangular prism, rod, octahedra, or rhombic dodecadhedra-shaped nanoparticles)〔Jones, M. R., et al., DNA-nanoparticle superlattices formed from anisotropic building blocks. ''Nat Mater'' 2010, 9 (11), 913-917.〕 utilize the nanoparticle core to arrange the linear nucleic acid components into functional forms. Indeed, it is the particle core that dictates the shape of the SNA, and to date, single-stranded and double-stranded versions of these materials have been created that consist of DNA, LNA, and RNA. SNAs should also not be confused with their monovalent analogues – individual particles coupled to a single DNA strand.〔Alivisatos, A. P., et al., Organization of 'nanocrystal molecules' using DNA. ''Nature'' 1996, 382 (6592), 609-611.〕 Such single strand-nanoparticle conjugate structures have led to interesting advances in their own right, but do not exhibit the unique properties of SNAs. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Spherical nucleic acid」の詳細全文を読む スポンサード リンク
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