Spherical nucleic acid

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.

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.

This polyvalency[further explanation needed], along with the high density and degree of orientation described above, helps explain why SNAs exhibit different properties than their lower-dimensional constituents (Fig.

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.

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.

[26] SNAs were shown to deliver small interfering RNA (siRNA) to treat glioblastoma multiforme in a proof-of-concept study using a mouse model.

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.

The arrangement of aptamers in an SNA geometry resulted in increased cellular uptake and detection of physiologically relevant changes in adenosine triphosphate (ATP) levels.

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.

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.

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.

[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.

[44] Particle analogs of electrons in colloidal crystals can be made using gold nanoparticles with greatly reduced size and numbers of attached DNA strands.

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.

Figure 1. Three important classes of nucleic acids: one-dimensional linear, two-dimensional circular, and three-dimensional spherical. [ 1 ]
Properties of Spherical Nucleic Acids versus Linear Nucleic Acids alt text
Figure 2. Properties of spherical nucleic acids (SNAs) versus linear nucleic acids. [ 1 ]
Core-filled and Core-less Spherical Nucleic Acids alt text
Figure 3. Gold nanoparticle filled and core-less spherical nucleic acid structures (SNAs). [ 1 ]
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 ]
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.
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 ]