Therapeutic potential of oligonucleotides expressing immunosuppressive TTAGGG motifs.

Dennis M. Klinman, Ihsan Gursel, Sven Klaschik, L. Dong, Debbie Currie, Hidekazu Shirota

Research output: Contribution to journalReview articlepeer-review

26 Citations (Scopus)

Abstract

Synthetic oligodeoxynucleotides (ODNs) expressing immunosuppressive TTAGGG motifs downregulate the production of proinflammatory and Th1 cytokines. The ability of these "suppressive ODNs" to slow or prevent the development of diseases characterized by over-exuberant immune stimulation was examined. Suppressive ODNs significantly reduced disease severity in murine models of arthritis, lupus, and LPS-induced toxic shock. These beneficial effects were accompanied by a significant reduction in serum autoantibody and cytokine levels. Underlying these protective effects was the ability of suppressive ODNs to bind to and prevent the phosphorylation of STAT1 and STAT4, thereby blocking the signaling cascade central to the initiation and/or perpetuation of these disease states. These findings suggest that suppressive ODNs might find use in the treatment of acute and chronic diseases characterized by excessive immune stimulation.

Original languageEnglish
Pages (from-to)87-95
Number of pages9
JournalAnnals of the New York Academy of Sciences
Volume1058
DOIs
Publication statusPublished - 2005 Nov
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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