Herein, we report a class of molecular spherical nucleic acid (SNA) nanostructures. These nano-sized single molecules are synthesized from T8 polyoctahedral silsesquioxane and buckminsterfullerene C60 scaffolds, modified with 8 and 12 pendant DNA strands, respectively. These conjugates have different DNA surface densities and thus exhibit different levels of nuclease resistance, cellular uptake, and gene regulation capabilities; the properties displayed by the C60 SNA conjugate are closer to those of conventional and prototypical gold nanoparticle SNAs. Importantly, the C60 SNA can serve as a single entity (no transfection agent required) antisense agent to efficiently regulate gene expression. The realization of molecularly pure forms of SNAs will open the door for studying the interactions of such structures with ligands and living cells with a much greater degree of control than the conventional polydisperse forms of SNAs.
Keywords: gene regulation; molecular nanoconjugates; oligonucleotides; spherical nucleic acids.