Spherical nucleic acids (SNAs) are nanostructures formed by chemically conjugating short linear strands of oligonucleotides to a nanoparticle template. When made with modified small interfering RNA (siRNA) duplexes, SNAs act as single-entity transfection and gene silencing agents and have been used as lead therapeutic constructs in several disease models. However, the manner in which modified siRNA duplex strands that comprise the SNA lead to gene silencing is not understood. Herein, a systematic analysis of siRNA biochemistry involving SNAs shows that Dicer cleaves the modified siRNA duplex from the surface of the nanoparticle, and the liberated siRNA subsequently functions in a way that is dependent on the canonical RNA interference mechanism. By leveraging this understanding, a class of SNAs was chemically designed which increases the siRNA content by an order of magnitude through covalent attachment of each strand of the duplex. As a consequence of increased nucleic acid content, this nanostructure architecture exhibits less cell cytotoxicity than conventional SNAs without a decrease in siRNA activity.
The programmed crystallization of particles into lowsymmetry lattices represents a major synthetic challenge in the field of colloidal crystal engineering. Herein, we report an approach to realizing such structures that relies on a library of low-symmetry Au nanoparticles, with synthetically adjustable dimensions and tunable aspect ratios. When modified with DNA ligands and used as building blocks for colloidal crystal engineering, these structures enable one to expand the types of accessible lattices and to answer mechanistic questions about phase transitions that break crystal symmetry. Indeed, crystals formed from a library of elongated rhombic dodecahedra yield a rich phase space, including low-symmetry lattices (body-centered tetragonal and hexagonal planar). Molecular dynamics simulations corroborate and provide insight into the origin of these phase transitions. In particular, we identify an unexpected asymmetry in the DNA shell, distinct from both the particle and lattice symmetries, which enables directional, nonclose-packed interactions.
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