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Proc Natl Acad Sci U S A. 2015 Mar 31;112(13):3892-7. doi: 10.1073/pnas.1502850112. Epub 2015 Mar 16.

Immunomodulatory spherical nucleic acids.

Author information

1
AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
2
Department of Chemistry, International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208.
3
Department of Chemistry, International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208 chadnano@northwestern.edu sgryaznov@aurasense.com.
4
AuraSense Therapeutics, LLC, Skokie, IL 60077; and chadnano@northwestern.edu sgryaznov@aurasense.com.

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.

KEYWORDS:

TLRs; immune regulation; nanotechnology; oligonucleotides; vaccines

PMID:
25775582
PMCID:
PMC4386353
DOI:
10.1073/pnas.1502850112
[Indexed for MEDLINE]
Free PMC Article

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