title: Immunomodulatory spherical nucleic acids.
abstract: Immunomodulatory 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. Immunomodulatory nucleic acids act by agonizing or antagonizing endosomal toll-like receptors (TLR3, TLR7/8, and TLR9), proteins involved in innate immune signaling. Immunomodulatory spherical nucleic acids (SNAs) that stimulate (immunostimulatory, IS-SNA) or regulate (immunoregulatory, IR-SNA) immunity by engaging TLRs have been designed, synthesized, and characterized. Compared with free oligonucleotides, IS-SNAs exhibit up to 80-fold increases in potency, 700-fold higher antibody titers, 400-fold higher cellular responses to a model antigen, and improved treatment of mice with lymphomas. IR-SNAs exhibit up to eightfold increases in potency and 30% greater reduction in fibrosis score in mice with nonalcoholic steatohepatitis (NASH). Given the clinical potential of SNAs due to their potency, defined chemical nature, and good tolerability, SNAs are attractive new modalities for developing immunotherapies.
authors.affiliation: AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
authors.forename: Aleksandar F
authors.initials: AF
authors.lastname: Radovic-Moreno
authors.affiliation: Department of Chemistry, International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208.
authors.forename: Natalia
authors.initials: N
authors.lastname: Chernyak
authors.affiliation: AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Mader
authors.affiliation: AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
authors.forename: Subbarao
authors.initials: S
authors.lastname: Nallagatla
authors.affiliation: AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Kang
authors.affiliation: Department of Chemistry, International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Hao
authors.affiliation: Department of Chemistry, International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208.
authors.forename: David A
authors.initials: DA
authors.lastname: Walker
authors.affiliation: AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
authors.forename: Tiffany L
authors.initials: TL
authors.lastname: Halo
authors.affiliation: Department of Chemistry, International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Merkel
authors.affiliation: AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
authors.forename: Clayton H
authors.initials: CH
authors.lastname: Rische
authors.affiliation: AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
authors.forename: Sagar
authors.initials: S
authors.lastname: Anantatmula
authors.affiliation: AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
authors.forename: Merideth
authors.initials: M
authors.lastname: Burkhart
authors.affiliation: Department of Chemistry, International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208 chadnano@northwestern.edu sgryaznov@aurasense.com.
authors.forename: Chad A
authors.initials: CA
authors.lastname: Mirkin
authors.affiliation: AuraSense Therapeutics, LLC, Skokie, IL 60077; and chadnano@northwestern.edu sgryaznov@aurasense.com.
authors.forename: Sergei M
authors.initials: SM
authors.lastname: Gryaznov
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry; D002460:Cell Line; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D008103:Liver Cirrhosis / Q000473:pathology; D008223:Lymphoma / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry; D009374:Neoplasms, Experimental / Q000628:therapy*; D065626:Non-alcoholic Fatty Liver Disease / Q000628:therapy*; D009690:Nucleic Acid Conformation; D009696:Nucleic Acids / Q000737:chemistry* / Q000627:therapeutic use; D009841:Oligonucleotides / Q000627:therapeutic use; D051193:Toll-Like Receptors / Q000819:agonists*
chemical_list: D000941:Antigens; D009696:Nucleic Acids; D009841:Oligonucleotides; D051193:Toll-Like Receptors
keywords: TLRs; immune regulation; nanotechnology; oligonucleotides; vaccines