Immunomodulatory Spherical Nucleic Acids*

Immuno-modulatory nucleic acids have extraordinary promise for treating disease, yet clinical progress has been limited by a lack of tools to safely increase activity in patients. Modulating immunity in a targeted and specific manner is an attractive approach for treating disease. The STAM mouse model has been developed as a small animal model that recapitulates important features of the human disease. The data convincingly show that spherical nucleic acids (SNAs) can be used as constructs for sequence-specific, potent, and therapeutically relevant immune-stimulation and immunoregulation. Importantly, such constructs outperform linear nonlipidated phosphodiester deoxynucleic acids due to a rapid cellular uptake, predominant accumulation in endosomes, and increased resistance to nucleases. Oligonucleotides were synthesized using automated solid support phosphoramidite synthesis. The activity of IR-SNAs was tested in the STAM mouse model of NASH.