Immunologic Research

, Volume 39, Issue 1, pp 4–14

Structural requirements and applications of inhibitory oligodeoxyribonucleotides

Authors

    • Graduate Program in Immunology, Carver College of MedicineUniversity of Iowa
  • Petar Lenert
    • Department of Internal Medicine, Carver College of MedicineUniversity of Iowa
Article

DOI: 10.1007/s12026-007-0065-4

Cite this article as:
Ashman, R.F. & Lenert, P. Immunol Res (2007) 39: 4. doi:10.1007/s12026-007-0065-4

Abstract

Synthetic oligodeoxyribonucleotides (ODN) bearing certain sequence characteristics mimic bacterial DNA by activating B cells and dendritic cells through Toll-like receptor (TLR) 9, an event that potentiates both humoral and cell-mediated immunity. ODN sharing some of the sequence characteristics of strong stimulatory (ST-) ODN, but substituting GGG for CGTT, competitively inhibit ST-ODN-driven events. An ODN with the same length and base composition as a strong ST-ODN, but lacking both ST- and IN-sequence requirements, has neither ST- nor IN-activity. Whereas, certain sequence changes strongly influence ST-ODN activity in human cells relative to mouse cells and B cells relative to non B cells, the strongest IN-ODN appear to work well in both species and multiple cell types. Converting from the natural phosphodiester backbone to a nuclease-resistant phosphorothioate backbone increases the sensitivity to ST-ODN about 2 logs and to IN-ODN 3 logs, while increasing the impact of critical base changes in ST-ODN and diminishing it in IN-ODN. Examples where IN-ODN have been used in vivo to interrupt autoimmune and other TLR-9-induced inflammatory states are described.

Keywords

Inhibitory oligonucleotidesTLR9Stimulatory oligonucleotidesAutoimmunityBacterial DNA

Copyright information

© Humana Press Inc. 2007