Sequence diversity in spherical nucleic acids

Abstract image

Synthesis and evaluation of spherical nucleic acids (SNAs) are described, which include two physically and chemically different classes of oligonucleotides (ODNs) in the programmed ratios. This SNA is a unifying agent that enters the stoichiometry of the same target cell and, as such, will enable it to control important cellular signaling and regulatory processes. To investigate the multiplicative effect of sequencing in such structures, we synthesized a DNA consisting of a mixture of class A and group C class C immunostimulatory ODNs that activate 9 different signaling pathways of two different receptor sequences, each in a sequence-specific manner. These dual CpG SNAs exhibit high cellular uptake and codelivation of the two ODNs, as compared to mixtures of linear ODN counterparts, and are highly correlated over time within the cell. In addition, dual CpG SNAs represent dendritic cell maturation, with relatively the same amount of oligonucleotides delivered in linear or SNA form but not in conjugate. Consequently, these structures constitute a platform for the development of oligonucleotide-based combination therapies that are highly customized with actions.