Molecular Spherical Nucleic Acids*
Spherical nucleic acids (SNAs) are inherently polydisperse due to variations in surface nucleic acid density, particle size, or both. This chapter describes 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. The chapter addresses the challenge of synthesizing and characterizing molecularly well defined SNA architectures from two different cores that allow for quantitative comparisons of structure–function relationships. In principle, SNA architectures provide the opportunity to create more chemically and biologically well-behaved and understood systems for both diagnostic and therapeutic uses.