ArticleInternational immunology2011
Optimal oligonucleotide sequences for TLR9 inhibitory activity in human cells: lack of correlation with TLR9 binding.
Article in International immunology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Review
- DNA Nanoflowers' Amelioration of Lupus Symptoms in Mice via Blockade of TLR7/9's Signal.International journal of molecular sciences · 2022Article
- Host-pathogen protein-nucleic acid interactions: A comprehensive review.Computational and structural biotechnology journal · 2022Review
- Potential of helper-dependent Adenoviral vectors in CRISPR-cas9-mediated lung gene therapy.Cell & bioscience · 2021Review
- SARS-CoV-2 will constantly sweep its tracks: a vaccine containing CpG motifs in 'lasso' for the multi-faced virus.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2020Article
- Mitochondrial DNA induces Foley catheter related bladder inflammation via Toll-like receptor 9 activation.Scientific reports · 2018Article
- Suppressive oligodeoxynucleotides containing TTAGGG motifs inhibit cGAS activation in human monocytes.European journal of immunology · 2018Article
- Sequence-Specific Sensing of Nucleic Acids.Trends in immunology · 2017Review
- Structure, mechanism and therapeutic utility of immunosuppressive oligonucleotides.Pharmacological research · 2016Review
- Guanine-modified inhibitory oligonucleotides efficiently impair TLR7- and TLR9-mediated immune responses of human immune cells.PloS one · 2015Article
- TLR9 activation is triggered by the excess of stimulatory versus inhibitory motifs present in Trypanosomatidae DNA.PLoS neglected tropical diseases · 2014Article
- RNA and imidazoquinolines are sensed by distinct TLR7/8 ectodomain sites resulting in functionally disparate signaling events.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Synthetic oligodeoxynucleotides containing suppressive TTAGGG motifs inhibit AIM2 inflammasome activation.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Human milk metagenome: a functional capacity analysis.BMC microbiology · 2013Article
- Design, synthesis and biological evaluation of novel antagonist compounds of Toll-like receptors 7, 8 and 9.Nucleic acids research · 2013Article
- CpG oligonucleotides bind TLR9 and RRM-containing proteins in Atlantic salmon (Salmo salar).BMC immunology · 2013Article
- TLR-9 contributes to the antiviral innate immune sensing of rodent parvoviruses MVMp and H-1PV by normal human immune cells.PloS one · 2013Article
- In vivo TLR9 inhibition attenuates CpG-induced myocardial dysfunction.Mediators of inflammation · 2013Article
- DNA binding to proteolytically activated TLR9 is sequence-independent and enhanced by DNA curvature.The EMBO journal · 2012Article
- Modulating toll-like receptor 7 and 9 responses as therapy for allergy and autoimmunity.Current allergy and asthma reports · 2012Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Toll-like receptor (TLR)9 performs our innate response to bacterial DNA, warning us of the presence of infection. Inhibitory oligodeoxyribonucleotides (INH-ODN) have been developed that selectively block activation of mouse TLR9. Their inhibitory motif consisting of CCx(not-C)(not-C)xxGGG (x = any base) also reduces anti-DNA antibodies in lupus mice. The current study demonstrates that this motif also provides the sequences required to block TLR9 in human B cells and human embryonic kidney (HEK) cells transfected with human TLR9. However, extending the sequence by four to five bases at the 5' end enhanced activity and this enhancement was greater when a phosphorothioate (pS) backbone replaced the native phosphodiester (pO) backbone. A series of pO-backbone INH-ODN representing a 500-fold range of activity in biologic assays was shown to cover less than a 2.5-fold range of avidity for binding human TLR9-Ig fusion protein, eliminating TLR9 ectodomain binding as the explanation for sequence-specific differences in biologic activity. With few exceptions, the relative activity of INH-ODN in Namalwa cells and HEK/human TLR9 cells was similar to that seen in mouse B cells. INH-ODN activity in human peripheral blood B cells correlated significantly with the cell line data. These results favor the conclusion that although the backbone determines strength of TLR9 binding, critical recognition of the INH-ODN sequence necessary for biologic activity is performed by a molecule that is not TLR9. These studies also identify the strongest INH-ODN for human B cells, helping to guide the selection of INH-ODN sequences for therapeutics in any situation where inflammation is enhanced by TLR9.
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Registered trials
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