Journal article
Structural requirements and applications of inhibitory oligodeoxyribonucleotides
Immunologic research, Vol.39(1-3), pp.4-14
2007
DOI: 10.1007/s12026-007-0065-4
PMID: 17917051
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.
Details
- Title: Subtitle
- Structural requirements and applications of inhibitory oligodeoxyribonucleotides
- Creators
- Robert F Ashman - Roy J. and Lucille A. Carver College of MedicinePetar Lenert - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Immunologic research, Vol.39(1-3), pp.4-14
- DOI
- 10.1007/s12026-007-0065-4
- PMID
- 17917051
- ISSN
- 0257-277X
- eISSN
- 1559-0755
- Grant note
- R01 AI 47374-04 / NIAID NIH HHS
- Language
- English
- Date published
- 2007
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984359916202771
Metrics
7 Record Views