IMMUNOMODULATORY SPHERICAL NUCLEIC ACIDS

摘要

Immunomodulatory nucleic acids have significant potential to treat disease, yet progress in the clinic has been limited by lack of tools to safely increase activity in patients. Immunomodulatory nucleic acids act by agonizing or antagonizing endosomal toll-like receptors (TLRs 3, 7/8, 9) a family of proteins involved in innate immune signaling. Novel immunomodulatory spherical nucleic acids (SNAs) that regulate (immunoregulatory, IR- SNA) immunity by engaging TLRs or anti TNF antisense oligonucleotides have been designed, synthesized and characterized. The nucleic acid-SNAs exhibit in some embodiments an 8-fold or greater increase in potency and 30% or greater reduction in fibrosis score in a subject with non-alcoholic steatohepatitis (NASH).