Figure 1. Three important classes of nucleic acids: one-dimensional linear, two-dimensional circular, and three-dimensional spherical.[1]

Spherical nucleic acids (SNAs)[1] are nanostructures that consist of a densely packed, highly oriented arrangement of linear nucleic acids in a three-dimensional, spherical geometry. This novel three-dimensional architecture is responsible for many of the SNA's novel chemical, biological, and physical properties that make it useful in biomedicine and materials synthesis. SNAs were first introduced in 1996[2] by Chad Mirkin’s group at Northwestern University.

Structure and function

The SNA structure typically consists of two components: a nanoparticle core and a nucleic acid shell. The nucleic acid shell is made up of short, synthetic oligonucleotides terminated with a functional group that can be utilized to attach them to the nanoparticle core. The dense loading of nucleic acids on the particle surface results in a characteristic radial orientation around the nanoparticle core, which minimizes repulsion between the negatively charged oligonucleotides.[3]

The first SNA consisted of a gold nanoparticle core with a dense shell of 3’ alkanethiol-terminated DNA strands.[2] Repeated additions of salt counterions were used to reduce the electrostatic repulsion between DNA strands and enable more efficient DNA packing on the nanoparticle surface. Since then, silver,[4] iron oxide,[5] silica,[6] and semiconductor[7] materials have also been used as inorganic cores for SNAs. Other core materials with increased biocompatibility, such FDA-approved PLGA polymer nanoparticles,[8] micelles,[9] liposomes,[10] and proteins[11] have also been used to prepare SNAs. Single-stranded and double-stranded versions of these materials have been created using, for example, DNA, LNA, and RNA.

One- and two-dimensional forms of nucleic acids (e.g., single strands, linear duplexes, and plasmids) (Fig. 1) are important biological machinery for the storage and transmission of genetic information. The specificity of DNA interactions through Watson–Crick base pairing provides the foundation for these functions. Scientists and engineers have been synthesizing and, in certain cases, mass-producing nucleic acids for decades to understand and exploit this elegant chemical recognition motif. The recognition abilities of nucleic acids can be enhanced when arranged in a spherical geometry, which allows for polyvalent interactions to occur. This polyvalency, along with the high density and degree of orientation described above, helps explain why SNAs exhibit different properties than their lower-dimensional constituents (Fig. 2).

Properties of Spherical Nucleic Acids versus Linear Nucleic Acids alt text
Figure 2. Properties of spherical nucleic acids (SNAs) versus linear nucleic acids.[1]

Over two decades of research has revealed that the properties of a SNA conjugate are a synergistic combination of those of the core and the shell. The core serves two purposes: 1) it imparts upon the conjugate novel physical and chemical properties (e.g., plasmonic,[2] catalytic,[12][13] magnetic,[14] luminescent[15]), and 2) it acts as a scaffold for the assembly and orientation of the nucleic acids. The nucleic acid shell imparts chemical and biological recognition abilities that include a greater binding strength,[16] cooperative melting behavior,[17] higher stability,[18] and enhanced cellular uptake without the use of transfection agents[19] (compared to the same sequence of linear DNA). It has been shown that one can crosslink the DNA strands at their base, and subsequently dissolve the inorganic core with KCN or I2 to create a core-less (hollow) form of SNA (Fig. 3, right),[12] which exhibits many of the same properties as the original polyvalent DNA gold nanoparticle conjugate (Fig. 3, left).

Core-filled and Core-less Spherical Nucleic Acids alt text
Figure 3. Gold nanoparticle filled and core-less spherical nucleic acid structures (SNAs).[1]

Due to their structure and function, SNAs occupy a materials space distinct from DNA nanotechnology and DNA origami,[20][21] (although both are important to the field of nucleic acid–guided programmable materials.[22] 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 their synthesis relies upon chemical bond formation between nanoparticles and DNA ligands. Furthermore, DNA origami uses DNA hybridization interactions to realize a final structure, whereas SNAs and other forms of three-dimensional nucleic acids (anisotropic structures templated with triangular prism, rod, octahedra, or rhombic dodecadhedra-shaped nanoparticles)[23] utilize the nanoparticle core to arrange the linear nucleic acid components into functional forms. It is the particle core that dictates the shape of the SNA. SNAs should also not be confused with their monovalent analogues – individual particles coupled to a single DNA strand.[24] Such single strand-nanoparticle conjugate structures have led to interesting advances in their own right, but do not exhibit the unique properties of SNAs.

Proposed applications

Intracellular gene regulation

Different Paths to Gene Regulation alt text
Figure 4. Nucleic acids arranged in a spherical geometry offer a fundamentally new path toward gene regulation. Benefits to this approach include the ability to enter cells without precomplexation with transfection agents, nuclease resistance, and minimal immune response.[1]

SNAs are being proposed as therapeutic materials. Despite their high negative charge, they are taken up by cells (also negatively charged) in high quantities without the need for positively charged co-carriers, and they are effective as gene regulation agents in both antisense and RNAi pathways (Fig. 4).[19][25] The proposed mechanism is that, unlike their linear counterparts, SNAs have the ability to complex scavenger receptor proteins to facilitate endocytosis.[26]

SNAs were shown to deliver small interfering RNA (siRNA) to treat glioblastoma multiforme in a proof-of-concept study using a mouse model.[27] The SNAs target Bcl2Like12, a gene overexpressed in glioblastoma tumors, and silences the oncogene. The SNAs injected intravenously cross the blood–brain barrier and find their target in the brain. In the animal model, the treatment resulted in a 20% increase in survival rate and 3 to 4-fold reduction in tumor size. This SNA-based therapeutic approach establishes a platform for treating a wide range of diseases with a genetic basis via digital drug design (where a new drug is made by changing the sequence of nucleic acid on a SNA).

Immunotherapy agents

SNA properties, such as enhanced cellular uptake, multivalent binding, and endosomal delivery, are desirable for the delivery of immunomodulatory nucleic acids. In particular, SNAs have been used deliver nucleic acids that agonize or antagonize toll-like receptors (proteins involved in innate immune signaling). The use of immunostimulatory SNAs has been shown to result in an 80-fold increase in potency, 700-fold higher antibody titers, 400-fold higher cellular responses to a model antigen, and improved treatment of mice with lymphomas compared to free oligonucleotides (not in SNA form).[28] SNAs have also been used by Mirkin to introduce the concept of “rational vaccinology,” that the chemical structure of an immunotherapy, as opposed to just the components alone, dictates its efficacy.[29] This concept has put a new structural focus on engineering vaccines for a wide range of diseases. This finding opens the possibility that, with previous treatments, researchers had the right components in the wrong structural arrangement – a particularly important lesson, especially in the context of COVID-19.

Verigene System from Nanosphere, Inc. alt text
Figure 5. The FDA-cleared Verigene system, originally developed and commercialized by Nanosphere, Inc., a company spun-out of research projects initiated in Mirkin's laboratory at Northwestern University. This system is now sold by Luminex, which acquired Nanosphere in 2016.

Intracellular probes

NanoFlares utilize the SNA architecture for intracellular mRNA detection.[30] In this design, alkanethiol-terminated antisense DNA strands (complementary to a target mRNA strand within cells) are attached to the surface of a gold nanoparticle. Fluorophore-labeled “reporter strands” are then hybridized to the SNA construct to form the NanoFlare. When the fluorophore labels are brought in close proximity of the gold surface, as controlled by programmable nucleic acid hybridization, their fluorescence is quenched (Fig. 6). After the cellular uptake of NanoFlares, the reporter strands can dehybridize from the NanoFlare when they are replaced by a longer, target mRNA sequence. Note that mRNA binding is thermodynamically favored since the strands holding the reporter sequence have greater overlap of their nucleotide sequence with the target mRNA. Upon reporter strand release, the dye fluorescence is no longer quenched by the gold nanoparticle core and increased fluorescence is observed. This method for RNA detection provides the only way to sort live cells based upon genetic content.

One publication questions the correlation between fluorescence intensities of SmartFlare probes and the levels of corresponding RNAs assessed by RT-qPCR.[31] Another paper has discussed SmartFlare applicability in early equine conceptuses, equine dermal fibroblast cells, and trophoblastic vesicles, finding that SmartFlares may only be applicable for certain uses.[32] Aptamer nanoflares have also been developed to bind to molecular targets other than intracellular mRNA. Aptamers, or oligonucleotide sequences that bind targets with high specificity and sensitivity, were first combined with the NanoFlare architecture in 2009. The arrangement of aptamers in an SNA geometry resulted in increased cellular uptake and detection of physiologically relevant changes in adenosine triphosphate (ATP) levels.[33]

Materials synthesis

SNAs have been utilized to develop an entire new field of materials science – one that focuses on using SNAs as synthetically programmable building blocks for the construction of colloidal crystals (Fig. 7). In 2011, a landmark paper was published in Science that defines a set of design rules for making superlattice structures of tailorable crystallographic symmetry and lattice parameters with sub-nm precision.[34] The complementary contact model (CCM) proposed in this work can be used to predict the thermodynamically favorable structure, which will maximize the number of hybridized DNA strands (contacts) between nanoparticles.

DNA-Gold Nanoparticle Superlattices alt text
Figure 7. Examples of the types of crystal structures that can be formed using design rules for preparing colloidal crystals. Note that the unit cell schematic, small angle x-ray scattering (SAXS) and electron microscopy data are shown for each example.[34]

Design rules for colloidal crystals engineered with DNA are analogous to Pauling's Rules for ionic crystals, but ultimately more powerful. For example, when using atomic or ionic building blocks in the construction of materials, the crystal structure, symmetry, and spacing are fixed by atomic radii and electronegativity. However, in the nanoparticle-based system, crystal structure can be tuned independent of the nanoparticle size and composition by simply adjusting the length and sequence of the attached DNA. As a result, nanoparticle building blocks with the SNA geometry are often referred to as “programmable atom equivalents” (PAEs).[35] This strategy has enabled the construction of novel crystal structures for several materials systems and even crystal structures with no mineral equivalents.[36] To date, over 50 different crystal symmetries have been achieved using colloidal crystal engineering with DNA.[37]

Lessons from atomic crystallization on macroscale structural features like crystal habit also translate to colloidal crystal engineering with DNA. The Wulff construction bound by the lowest surface energy facets can be achieved for certain nanoparticle symmetries by using a slow cooling crystallization method. This concept was first demonstrated with a body-centered cubic symmetry, where the densest-packed planes were exposed on the surface resulting in a rhombic dodecahedron crystal habit.[38] Other habits such as octrahedra, cubes, or hexagonal prisms have been realized using anisotropic nanoparticles or non-cubic unit cells.[39] Colloidal crystals have also been grown through heterogeneous growth on DNA-functionalized substrates, where lithography can be used to define templates or specific crystal orientations.[40]

Introducing anisotropy to the underlying nanoparticle core has also expanded the scope of structures that can be programmed using DNA. When shorter DNA designs are used with anisotropic nanoparticle cores, directional bonding interactions between DNA on particle facets can drive the formation of specific lattice symmetries and crystal habits.[23] Localizing DNA to specific parts of a particle building block can also be achieved using biological cores, such as proteins with chemically anisotropic surfaces.[41] Directional interactions and valency have been used to direct the formation of new lattice symmetries with protein cores that are difficult to access with inorganic particles.[42] DNA origami frameworks borrowed from the structural DNA nanotechnology community have also been applied as cages for inorganic nanoparticle cores to impart valency and direct the formation of new lattice symmetries.[43]

Colloidal crystals engineered using DNA often form crystal structures similar to ionic compounds, but a new method to access colloidal crystals with metallic-like bonding was recently reported in Science.[44] Particle analogs of electrons in colloidal crystals can be made using gold nanoparticles with greatly reduced size and numbers of attached DNA strands. When combined with typical PAEs, these “electron equivalents” (EEs) roam through the lattice like electrons do in metals. This discovery can be used to access new alloy or intermetallic structures in colloidal crystals.

The ability to place nanoparticles of any composition and shape at any location in a well-defined crystalline lattice with nm-scale precision should have far-reaching implications in areas ranging from catalysis to photonics to energy. Catalytically active and porous materials have been assembled using DNA,[45] and colloidal crystals engineered with DNA can also function as plasmonic photonic crystals with applications in nanoscale optical devices.[46] Chemical stimuli, such as salt concentration,[47] pH,[48] or solvent,[49] and physical stimuli like light[50] have been harnessed to design stimuli-responsive colloidal crystals using DNA-mediated assembly.

Economic impact

The economic impact of SNA technology is substantial. Three companies have been founded that are based on SNA technology – Nanosphere in 2000, AuraSense in 2009, and AuraSense Therapeutics (now Exicure, Inc.) in 2011. Hundreds of millions of dollars have been invested in these companies and they have employed hundreds of people. The SmartFlares were commercialised by Merck Millipore between 2013 and 2018 for the detection of mRNAs in life cells before being withdrawn as they in fact do not detect mRNAs in life cells.[51] Nanosphere was one of the first nanotechnology-based biotechnology firms to go public in late 2007. It burnt through over $412.5 million since inception[52] before being sold for $58M in 2016 to Luminex.[53] The FDA-cleared Verigene system is now sold by Luminex with accompanying FDA-cleared panel assays for bloodstream, respiratory tract, and gastrointestinal tract infections. It is being used for COVID-19 surveillance. Exicure went public in 2018 and is listed on the Nasdaq (XCUR). At the end of 2022, it was on its "death spiral".[54]

References

  1. 1 2 3 4 5 Cutler JI, Auyeung E, Mirkin CA (January 2012). "Spherical nucleic acids". Journal of the American Chemical Society. 134 (3): 1376–1391. doi:10.1021/ja209351u. PMID 22229439. S2CID 13676422.
  2. 1 2 3 Mirkin CA, Letsinger RL, Mucic RC, Storhoff JJ (August 1996). "A DNA-based method for rationally assembling nanoparticles into macroscopic materials". Nature. 382 (6592): 607–609. Bibcode:1996Natur.382..607M. doi:10.1038/382607a0. PMID 8757129. S2CID 4284601.
  3. ↑ Hill HD, Millstone JE, Banholzer MJ, Mirkin CA (February 2009). "The role radius of curvature plays in thiolated oligonucleotide loading on gold nanoparticles". ACS Nano. 3 (2): 418–424. doi:10.1021/nn800726e. PMC 3241534. PMID 19236080.
  4. ↑ Lee JS, Lytton-Jean AK, Hurst SJ, Mirkin CA (July 2007). "Silver nanoparticle-oligonucleotide conjugates based on DNA with triple cyclic disulfide moieties". Nano Letters. 7 (7): 2112–2115. Bibcode:2007NanoL...7.2112L. doi:10.1021/nl071108g. PMC 3200546. PMID 17571909.
  5. ↑ Cutler JI, Zheng D, Xu X, Giljohann DA, Mirkin CA (April 2010). "Polyvalent oligonucleotide iron oxide nanoparticle "click" conjugates". Nano Letters. 10 (4): 1477–1480. Bibcode:2010NanoL..10.1477C. doi:10.1021/nl100477m. PMC 2874426. PMID 20307079.
  6. ↑ Young KL, Scott AW, Hao L, Mirkin SE, Liu G, Mirkin CA (July 2012). "Hollow spherical nucleic acids for intracellular gene regulation based upon biocompatible silica shells". Nano Letters. 12 (7): 3867–3871. Bibcode:2012NanoL..12.3867Y. doi:10.1021/nl3020846. PMC 3397824. PMID 22725653.
  7. ↑ Zhang C, Macfarlane RJ, Young KL, Choi CH, Hao L, Auyeung E, et al. (August 2013). "A general approach to DNA-programmable atom equivalents". Nature Materials. 12 (8): 741–746. Bibcode:2013NatMa..12..741Z. doi:10.1038/nmat3647. PMID 23685863. S2CID 6028400.
  8. ↑ Zhu S, Xing H, Gordiichuk P, Park J, Mirkin CA (May 2018). "PLGA Spherical Nucleic Acids". Advanced Materials. 30 (22): e1707113. Bibcode:2018AdM....3007113Z. doi:10.1002/adma.201707113. PMC 6029717. PMID 29682820.
  9. ↑ Banga RJ, Meckes B, Narayan SP, Sprangers AJ, Nguyen ST, Mirkin CA (March 2017). "Cross-Linked Micellar Spherical Nucleic Acids from Thermoresponsive Templates". Journal of the American Chemical Society. 139 (12): 4278–4281. doi:10.1021/jacs.6b13359. PMC 5493153. PMID 28207251.
  10. ↑ Banga RJ, Chernyak N, Narayan SP, Nguyen ST, Mirkin CA (July 2014). "Liposomal spherical nucleic acids". Journal of the American Chemical Society. 136 (28): 9866–9869. doi:10.1021/ja504845f. PMC 4280063. PMID 24983505.
  11. ↑ Brodin JD, Auyeung E, Mirkin CA (April 2015). "DNA-mediated engineering of multicomponent enzyme crystals". Proceedings of the National Academy of Sciences of the United States of America. 112 (15): 4564–4569. doi:10.1073/pnas.1503533112. PMC 4403210. PMID 25831510.
  12. 1 2 Cutler JI, Zhang K, Zheng D, Auyeung E, Prigodich AE, Mirkin CA (June 2011). "Polyvalent nucleic acid nanostructures". Journal of the American Chemical Society. 133 (24): 9254–9257. doi:10.1021/ja203375n. PMC 3154250. PMID 21630678..
  13. ↑ Taton TA, Mirkin CA, Letsinger RL (September 2000). "Scanometric DNA array detection with nanoparticle probes". Science. 289 (5485): 1757–1760. Bibcode:2000Sci...289.1757T. doi:10.1126/science.289.5485.1757. PMID 10976070. S2CID 24119488.
  14. ↑ Park SS, Urbach ZJ, Brisbois CA, Parker KA, Partridge BE, Oh T, et al. (January 2020). "DNA- and Field-Mediated Assembly of Magnetic Nanoparticles into High-Aspect Ratio Crystals". Advanced Materials. 32 (4): e1906626. Bibcode:2020AdM....3206626P. doi:10.1002/adma.201906626. PMID 31814172. S2CID 208955629.
  15. ↑ Michell GP, Mirkin CA, Letsinger RL (2005). "Programmed Assembly of DNA Functionalized Quantum Dots [J]". Journal of Crystal Growth. 280 (35): 300–304. doi:10.1021/ja991662v.
  16. ↑ Lytton-Jean AK, Mirkin CA (September 2005). "A thermodynamic investigation into the binding properties of DNA functionalized gold nanoparticle probes and molecular fluorophore probes". Journal of the American Chemical Society. 127 (37): 12754–12755. doi:10.1021/ja052255o. PMID 16159241. S2CID 44772135.
  17. ↑ Hurst SJ, Hill HD, Mirkin CA (September 2008). ""Three-dimensional hybridization" with polyvalent DNA-gold nanoparticle conjugates". Journal of the American Chemical Society. 130 (36): 12192–12200. doi:10.1021/ja804266j. PMC 8191498. PMID 18710229.
  18. ↑ Seferos DS, Prigodich AE, Giljohann DA, Patel PC, Mirkin CA (January 2009). "Polyvalent DNA nanoparticle conjugates stabilize nucleic acids". Nano Letters. 9 (1): 308–311. Bibcode:2009NanoL...9..308S. doi:10.1021/nl802958f. PMC 3918421. PMID 19099465.
  19. 1 2 Rosi NL, Giljohann DA, Thaxton CS, Lytton-Jean AK, Han MS, Mirkin CA (May 2006). "Oligonucleotide-modified gold nanoparticles for intracellular gene regulation". Science. 312 (5776): 1027–1030. Bibcode:2006Sci...312.1027R. doi:10.1126/science.1125559. PMID 16709779. S2CID 28476438.
  20. ↑ Han D, Pal S, Nangreave J, Deng Z, Liu Y, Yan H (April 2011). "DNA origami with complex curvatures in three-dimensional space". Science. 332 (6027): 342–346. Bibcode:2011Sci...332..342H. doi:10.1126/science.1202998. PMID 21493857. S2CID 22210988.
  21. ↑ Seeman NC (January 2003). "DNA in a material world". Nature. 421 (6921): 427–431. Bibcode:2003Natur.421..427S. doi:10.1038/nature01406. PMID 12540916. S2CID 4335806.
  22. ↑ Jones MR, Seeman NC, Mirkin CA (February 2015). "Nanomaterials. Programmable materials and the nature of the DNA bond". Science. 347 (6224): 1260901. doi:10.1126/science.1260901. PMID 25700524. S2CID 206562591.
  23. 1 2 Jones MR, Macfarlane RJ, Lee B, Zhang J, Young KL, Senesi AJ, Mirkin CA (November 2010). "DNA-nanoparticle superlattices formed from anisotropic building blocks". Nature Materials. 9 (11): 913–917. Bibcode:2010NatMa...9..913J. doi:10.1038/nmat2870. PMID 20890281. S2CID 6277948.
  24. ↑ Alivisatos AP, Johnsson KP, Peng X, Wilson TE, Loweth CJ, Bruchez MP, Schultz PG (August 1996). "Organization of 'nanocrystal molecules' using DNA". Nature. 382 (6592): 609–611. Bibcode:1996Natur.382..609A. doi:10.1038/382609a0. PMID 8757130. S2CID 2024148.
  25. ↑ Giljohann DA, Seferos DS, Prigodich AE, Patel PC, Mirkin CA (February 2009). "Gene regulation with polyvalent siRNA-nanoparticle conjugates". Journal of the American Chemical Society. 131 (6): 2072–2073. doi:10.1021/ja808719p. PMC 2843496. PMID 19170493.
  26. ↑ Choi CH, Hao L, Narayan SP, Auyeung E, Mirkin CA (May 2013). "Mechanism for the endocytosis of spherical nucleic acid nanoparticle conjugates". Proceedings of the National Academy of Sciences of the United States of America. 110 (19): 7625–7630. Bibcode:2013PNAS..110.7625C. doi:10.1073/pnas.1305804110. PMC 3651452. PMID 23613589.
  27. ↑ Jensen SA, Day ES, Ko CH, Hurley LA, Luciano JP, Kouri FM, et al. (October 2013). "Spherical nucleic acid nanoparticle conjugates as an RNAi-based therapy for glioblastoma". Science Translational Medicine. 5 (209): 209ra152. doi:10.1126/scitranslmed.3006839. PMC 4017940. PMID 24174328.
  28. ↑ Radovic-Moreno AF, Chernyak N, Mader CC, Nallagatla S, Kang RS, Hao L, et al. (March 2015). "Immunomodulatory spherical nucleic acids". Proceedings of the National Academy of Sciences of the United States of America. 112 (13): 3892–3897. Bibcode:2015PNAS..112.3892R. doi:10.1073/pnas.1502850112. PMC 4386353. PMID 25775582.
  29. ↑ Wang S, Qin L, Yamankurt G, Skakuj K, Huang Z, Chen PC, et al. (May 2019). "Rational vaccinology with spherical nucleic acids". Proceedings of the National Academy of Sciences of the United States of America. 116 (21): 10473–10481. Bibcode:2019PNAS..11610473W. doi:10.1073/pnas.1902805116. PMC 6535021. PMID 31068463.
  30. ↑ Seferos DS, Giljohann DA, Hill HD, Prigodich AE, Mirkin CA (December 2007). "Nano-flares: probes for transfection and mRNA detection in living cells". Journal of the American Chemical Society. 129 (50): 15477–15479. doi:10.1021/ja0776529. PMC 3200543. PMID 18034495.
  31. ↑ Czarnek M, Bereta J (September 2017). "SmartFlares fail to reflect their target transcripts levels". Scientific Reports. 7 (1): 11682. Bibcode:2017NatSR...711682C. doi:10.1038/s41598-017-11067-6. PMC 5600982. PMID 28916792.
  32. ↑ Budik S, Tschulenk W, Kummer S, Walter I, Aurich C (October 2017). "Evaluation of SmartFlare probe applicability for verification of RNAs in early equine conceptuses, equine dermal fibroblast cells and trophoblastic vesicles". Reproduction, Fertility, and Development. 29 (11): 2157–2167. doi:10.1071/RD16362. PMID 28248633.
  33. ↑ Zheng D, Seferos DS, Giljohann DA, Patel PC, Mirkin CA (September 2009). "Aptamer nano-flares for molecular detection in living cells". Nano Letters. 9 (9): 3258–3261. Bibcode:2009NanoL...9.3258Z. doi:10.1021/nl901517b. PMC 3200529. PMID 19645478.
  34. 1 2 Macfarlane RJ, Lee B, Jones MR, Harris N, Schatz GC, Mirkin CA (October 2011). "Nanoparticle superlattice engineering with DNA". Science. 334 (6053): 204–208. Bibcode:2011Sci...334..204M. doi:10.1126/science.1210493. PMID 21998382. S2CID 1626420.
  35. ↑ Macfarlane RJ, O'Brien MN, Petrosko SH, Mirkin CA (May 2013). "Nucleic acid-modified nanostructures as programmable atom equivalents: forging a new "table of elements"". Angewandte Chemie. 52 (22): 5688–5698. doi:10.1002/anie.201209336. PMID 23640804. S2CID 21929457.
  36. ↑ Auyeung E, Cutler JI, Macfarlane RJ, Jones MR, Wu J, Liu G, et al. (December 2011). "Synthetically programmable nanoparticle superlattices using a hollow three-dimensional spacer approach". Nature Nanotechnology. 7 (1): 24–28. doi:10.1038/nnano.2011.222. PMID 22157725. S2CID 32732649.
  37. ↑ Laramy CR, O'Brien MN, Mirkin CA (2019). "Crystal engineering with DNA". Nature Reviews Materials. 4 (3): 201–224. Bibcode:2019NatRM...4..201L. doi:10.1038/s41578-019-0087-2. S2CID 86787635.
  38. ↑ Auyeung E, Li TI, Senesi AJ, Schmucker AL, Pals BC, de la Cruz MO, Mirkin CA (January 2014). "DNA-mediated nanoparticle crystallization into Wulff polyhedra". Nature. 505 (7481): 73–77. Bibcode:2014Natur.505...73A. doi:10.1038/nature12739. PMID 24284632. S2CID 4455259.
  39. ↑ O'Brien MN, Lin HX, Girard M, Olvera de la Cruz M, Mirkin CA (November 2016). "Programming Colloidal Crystal Habit with Anisotropic Nanoparticle Building Blocks and DNA Bonds". Journal of the American Chemical Society. 138 (44): 14562–14565. doi:10.1021/jacs.6b09704. PMID 27792331. S2CID 11441382.
  40. ↑ Lin QY, Mason JA, Li Z, Zhou W, O'Brien MN, Brown KA, et al. (February 2018). "Building superlattices from individual nanoparticles via template-confined DNA-mediated assembly". Science. 359 (6376): 669–672. Bibcode:2018Sci...359..669L. doi:10.1126/science.aaq0591. PMID 29348364. S2CID 3544406.
  41. ↑ McMillan JR, Hayes OG, Winegar PH, Mirkin CA (July 2019). "Protein Materials Engineering with DNA". Accounts of Chemical Research. 52 (7): 1939–1948. doi:10.1021/acs.accounts.9b00165. PMID 31199115. S2CID 189816251.
  42. ↑ Hayes OG, McMillan JR, Lee B, Mirkin CA (July 2018). "DNA-Encoded Protein Janus Nanoparticles". Journal of the American Chemical Society. 140 (29): 9269–9274. doi:10.1021/jacs.8b05640. OSTI 1475554. PMID 29989807. S2CID 51610571.
  43. ↑ Liu W, Tagawa M, Xin HL, Wang T, Emamy H, Li H, et al. (February 2016). "Diamond family of nanoparticle superlattices". Science. 351 (6273): 582–586. Bibcode:2016Sci...351..582L. doi:10.1126/science.aad2080. PMC 5275765. PMID 26912698.
  44. ↑ Girard M, Wang S, Du JS, Das A, Huang Z, Dravid VP, et al. (June 2019). "Particle analogs of electrons in colloidal crystals". Science. 364 (6446): 1174–1178. Bibcode:2019Sci...364.1174G. doi:10.1126/science.aaw8237. PMC 8237478. PMID 31221857..
  45. ↑ Auyeung E, Morris W, Mondloch JE, Hupp JT, Farha OK, Mirkin CA (February 2015). "Controlling structure and porosity in catalytic nanoparticle superlattices with DNA". Journal of the American Chemical Society. 137 (4): 1658–1662. doi:10.1021/ja512116p. PMID 25611764. S2CID 4798544.
  46. ↑ Sun L, Lin H, Kohlstedt KL, Schatz GC, Mirkin CA (July 2018). "Design principles for photonic crystals based on plasmonic nanoparticle superlattices". Proceedings of the National Academy of Sciences of the United States of America. 115 (28): 7242–7247. Bibcode:2018PNAS..115.7242S. doi:10.1073/pnas.1800106115. PMC 6048504. PMID 29941604.
  47. ↑ Samanta D, Iscen A, Laramy CR, Ebrahimi SB, Bujold KE, Schatz GC, Mirkin CA (December 2019). "Multivalent Cation-Induced Actuation of DNA-Mediated Colloidal Superlattices". Journal of the American Chemical Society. 141 (51): 19973–19977. doi:10.1021/jacs.9b09900. PMC 7183202. PMID 31840998.
  48. ↑ Zhu J, Kim Y, Lin H, Wang S, Mirkin CA (April 2018). "pH-Responsive Nanoparticle Superlattices with Tunable DNA Bonds". Journal of the American Chemical Society. 140 (15): 5061–5064. doi:10.1021/jacs.8b02793. PMID 29624374. S2CID 4936133.
  49. ↑ Mason JA, Laramy CR, Lai CT, O'Brien MN, Lin QY, Dravid VP, et al. (July 2016). "Contraction and Expansion of Stimuli-Responsive DNA Bonds in Flexible Colloidal Crystals". Journal of the American Chemical Society. 138 (28): 8722–8725. doi:10.1021/jacs.6b05430. OSTI 1418572. PMID 27402303. S2CID 207168694.
  50. ↑ Zhu J, Lin H, Kim Y, Yang M, Skakuj K, Du JS, et al. (February 2020). "Light-Responsive Colloidal Crystals Engineered with DNA". Advanced Materials. 32 (8): e1906600. Bibcode:2020AdM....3206600Z. doi:10.1002/adma.201906600. PMC 7061716. PMID 31944429.
  51. ↑ Czarnek M, Bereta J (September 2017). "SmartFlares fail to reflect their target transcripts levels". Scientific Reports. 7 (1): 11682. Bibcode:2017NatSR...711682C. doi:10.1038/s41598-017-11067-6. PMC 5600982. PMID 28916792.
  52. ↑ Nanalyze (2 February 2015). "Things Are Not Well at Nanosphere (NSPH)". Nanalyze. Retrieved 14 January 2023.
  53. ↑ Gomez A. "Nanosphere (NSPH) Stock Skyrockets on $58 Million Luminex Deal". TheStreet. Retrieved 14 January 2023.
  54. ↑ Taylor NP (14 December 2022). "AbbVie, Ipsen exit R&D deals to cap off lousy year for Exicure". Fierce Biotech. Retrieved 14 January 2023.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.