Molecular spherical nucleic acids

Significance Spherical nucleic acids (SNAs) made thus far are inherently polydisperse due to variations in surface nucleic acid density, particle size, or both. In this article, we describe the synthesis and characterization of two types of molecular SNAs with precise numbers of surface DNA strands using T8 polyoctahedral silsesquioxane and buckminsterfullerene C60 scaffolds. The surface DNA densities for these molecular structures fall inside the range of typical SNAs, which allows them to exhibit SNA-related properties, including enhanced cellular uptake and the ability to function as a gene regulation agent. With a route to molecularly pure SNAs opened, it becomes possible to use them to unveil the molecular details of SNA interactions with complementary ligands and living systems.