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Immunomodulatory spherical nucleic acids.
Radovic-Moreno, Aleksandar F; Chernyak, Natalia; Mader, Christopher C; Nallagatla, Subbarao; Kang, Richard S; Hao, Liangliang; Walker, David A; Halo, Tiffany L; Merkel, Timothy J; Rische, Clayton H; Anantatmula, Sagar; Burkhart, Merideth; Mirkin, Chad A; Gryaznov, Sergei M.
Afiliación
  • Radovic-Moreno AF; AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
  • Chernyak N; Department of Chemistry, International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208.
  • Mader CC; AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
  • Nallagatla S; AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
  • Kang RS; AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
  • Hao L; Department of Chemistry, International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208.
  • Walker DA; Department of Chemistry, International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208.
  • Halo TL; AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
  • Merkel TJ; Department of Chemistry, International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208.
  • Rische CH; AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
  • Anantatmula S; AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
  • Burkhart M; AuraSense Therapeutics, LLC, Skokie, IL 60077; and.
  • Mirkin CA; Department of Chemistry, International Institute for Nanotechnology, Northwestern University, Evanston, IL 60208 chadnano@northwestern.edu sgryaznov@aurasense.com.
  • Gryaznov SM; AuraSense Therapeutics, LLC, Skokie, IL 60077; and chadnano@northwestern.edu sgryaznov@aurasense.com.
Proc Natl Acad Sci U S A ; 112(13): 3892-7, 2015 Mar 31.
Article en En | MEDLINE | ID: mdl-25775582
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácidos Nucleicos / Receptores Toll-Like / Enfermedad del Hígado Graso no Alcohólico / Neoplasias Experimentales Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2015 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácidos Nucleicos / Receptores Toll-Like / Enfermedad del Hígado Graso no Alcohólico / Neoplasias Experimentales Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2015 Tipo del documento: Article
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