Immunomodulatory Spherical Nucleic Acids*
Immunomodulatory nucleic acids act by agonizing or antagonizing endosomal toll-like receptors (TLR3, TLR7/8, and TLR9), proteins involved in innate immune signaling. This chapter shows that by organizing immunomodulatory nucleic acids into spherical nucleic acid (SNA) form, significant increases in activity are observed. It underscores the importance of the spatial orientation and presentation of oligonucleotides in the design of novel immunomodulators. The chapter describes an unreported class of immunomodulatory SNAs, which can be used either for stimulating (immunostimulatory, IS-SNAs) or regulating (immunoregulatory, IR-SNA) immune responses. It demonstrate that the properties of SNAs lead to significant activity improvements compared with free oligonucleotide counterparts for both IS-SNAs and IR-SNAs in vitro and in vivo.