Immunomodulatory spherical nucleic acids

Aleksandar F. Radovic-Moreno, Natalia Chernyak, Christopher C. Mader, Subbarao Nallagatla, Richard S. Kang, Liangliang Hao, David A. Walker, Tiffany L. Halo, Timothy J. Merkel, Clayton H. Rische, Sagar Anantatmula, Merideth Burkhart, Chad A. Mirkin, Sergei M. Gryaznov*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3892-3897
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number13
DOIs
StatePublished - Mar 31 2015

Keywords

  • Immune regulation
  • Nanotechnology
  • Oligonucleotides
  • TLRs
  • Vaccines

ASJC Scopus subject areas

  • General

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