Therapeutic potential of anti-interleukin-17A aptamer: suppression of interleukin-17A signaling and attenuation of autoimmunity in two mouse models

Arthritis Rheum. 2011 Feb;63(2):455-66. doi: 10.1002/art.30108.


Objective: The proinflammatory cytokine interleukin-17A (IL-17A) is produced primarily by the CD4+ T cell subset called Th17 cells, which is involved in host defense, inflammation, and autoimmune disorders. This study was undertaken to investigate the effect of a high-affinity RNA molecule, called an aptamer, against human IL-17A on IL-17A-induced signal transduction in vitro and its anti-autoimmune efficacy in vivo in 2 mouse models of inflammation.

Methods: By screening a large library of nuclease-resistant RNA oligonucleotides, we selected an RNA aptamer, Apt21-2, that binds human and mouse IL-17 and blocks the interaction between IL-17A and its receptor. The inhibition of IL-17A-mediated phosphorylation and marker protein production was analyzed in human and mouse cells. Mice with glucose-6-phosphate isomerase (GPI)-induced rheumatoid arthritis and myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis were used to assess efficacy.

Results: Apt21-2 prevented efficient phosphorylation of the IL-17A signaling factors IκB and JNK and inhibited the production of IL-6 in human and mouse cells. A PEGylated form of Apt21-2 (PEG21-2idT) exhibited a 50% inhibition concentration (IC(50) ) in the range of 1-2 nM and 70-80 nM in human and mouse cells, respectively. When administered immediately after immunization with GPI or MOG, PEG21-2idT inhibited in a dose-dependent manner the development of arthritic or neurologic symptoms. Significantly, PEG21-2idT slowed the progression of arthritis when administered after the onset of GPI-induced arthritis.

Conclusion: Our findings indicate that the chemically processed anti-IL-17A aptamer PEG21-2idT inhibits the actions of IL-17A as well as the development of autoimmunity in 2 mouse models of inflammation. These results offer for the first time an aptamer-based therapeutic approach to the treatment of Th17 cell-mediated autoimmune disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aptamers, Nucleotide / pharmacology*
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / immunology
  • Autoimmunity / drug effects*
  • Autoimmunity / immunology
  • Disease Models, Animal
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Female
  • Glucose-6-Phosphate Isomerase / immunology
  • Humans
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / genetics*
  • Interleukin-17 / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • SELEX Aptamer Technique
  • Signal Transduction / drug effects


  • Aptamers, Nucleotide
  • Interleukin-17
  • Glucose-6-Phosphate Isomerase