New macro-molecular constructs, called Spherical Nucleic Acids (SNAs), were designed, synthesized and studied as sequence-specific and versatile TLR-addressed regulators of innate immune system.  These multi-valented SNAs consist of two essential components: a mono-dispersed colloidal gold nanoparticle-based core, and nucleic acids, which are covalently attached to the core surface. These nucleic acid pharmacophore exert their activity via aptamer-type interactions with TLR receptors, in either agonistic � ImmunoStimulatory  (is-SNAs), or antagonistic � ImmunoRepressive (ir-SNAs) manner. The SNAs exhibit interesting and unexpected activity both in vitro and in vivo, which marks them as attractive candidates for further therapeutic development. Thus, cellular uptake, stability, and overall TLR9 activating efficacy of the SNAs with natural CpG-motif containing phosphodiester oligonucleotide conjugates were significantly improved vis-a-vis un-conjugated oligo counterparts. A detailed overview of the SNA synthesis, structure, specific gene and therapeutically important pathway regulatory activity in vitro and in vivo will be presented.

Spherical nucleic acids (SNAs) as potent immuno modulatory agents

248th National Meeting (2014)

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