TY - JOUR
T1 - Immunomodulatory spherical nucleic acids
AU - Radovic-Moreno, Aleksandar F.
AU - Chernyak, Natalia
AU - Mader, Christopher C.
AU - Nallagatla, Subbarao
AU - Kang, Richard S.
AU - Hao, Liangliang
AU - Walker, David A.
AU - Halo, Tiffany L.
AU - Merkel, Timothy J.
AU - Rische, Clayton H.
AU - Anantatmula, Sagar
AU - Burkhart, Merideth
AU - Mirkin, Chad A.
AU - Gryaznov, Sergei M.
PY - 2015/3/31
Y1 - 2015/3/31
N2 - 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.
AB - 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.
KW - Immune regulation
KW - Nanotechnology
KW - Oligonucleotides
KW - TLRs
KW - Vaccines
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U2 - 10.1073/pnas.1502850112
DO - 10.1073/pnas.1502850112
M3 - Article
C2 - 25775582
AN - SCOPUS:84961288005
SN - 0027-8424
VL - 112
SP - 3892
EP - 3897
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 13
ER -
