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United States 

Dual-iODN (class I) (endotoxin-free) (synthetic) (BULK)

Inhibitor of TLR7 and TLR9
ALX-746-355-M001 1 mg 325.00 USD
For a smaller pack size, please see Prod. No. ALX-746-255.
Inhibitory iODN oligodeoxynucleotide with phosphorothioate backbone. Sequence of an inhibitory ODN for in vivo use in rodents (50-150µg per injection): prototype class I that potently inhibits TLR9 and TLR7 signaling.

Product Specification

Sequence:5’-tgctcctggaggggttgt-3’(lower case letters indicate phosphorothioate linkage).
MW:5867 (ammonium salt)
Quantity:~170nmol (1'000µg). Working concentration depends upon concentration, type and MW of stimulating CpG ODN, the cellular system and read-out used. Titrate at 3-10 fold molar excess for inhibition.
Formulation:Lyophilized. Sterile.
Endotoxin Content:<0.0002EU/µg (LAL test; BioWhittaker)
Reconstitution:For a 200µM stock solution, dissolve the total vial content in 852µl endotoxin-free ddWater (Prod. No. ALX-505-008) or endotoxin-free PBS (Prod. No. ALX-505-007). To obtain optimal dissolving we recommend the following procedure:
- Add 50% of the solvent and let dissolve for 10 min.
- Add remaining 50% of the solvent and mix thoroughly.
- Moderate warming may aid dissolving.
Long Term Storage:+4°C
Use/Stability:Aqueous stock solution is stable for 1 day when stored at +4°C.
Miscellaneous/General:Several groups have studied the sequence requirements, specificity, signalling pathways and kinetics of the TLR (Toll-like receptor) 9 suppression by ‘inhibitory DNA motifs’, which led to a revised classification of iODNs, that is independent of the previously thought species preference.
Class I: G-stretch ODNs: TLR9-specific competitors, some iODNs may also affect TLR7 and TLR8 signaling
Class II: ODNs with telomeric repeats: TLR-independent inhibitors of STAT signalling (cellular uptake via an “ODN receptor”?)
Class III: Inhibitors of DNA uptake in a sequence independent manner
Class IV: Long phosphorothioate ODNs as direct competitors of TLR9 signaling in a sequence independent manner
Slightly modified phosphodiester versions of the most potent inhibitory ODNs were also able to profoundly block the immune activation of macrophages and proved to be valuable tools for in vivo use in experimental animal models of inflammatory and auto-immune diseases.
Background / Technical Information:Includes 1 vial of ddWater (endotoxin-free) (Prod. No. ALX-505-008).

Product Literature References

Inhibition of Toll-like receptor-7 (TLR-7) or TLR-7 plus TLR-9 attenuates glomerulonephritis and lung injury in experimental lupus: R.D. Pawar, et al.; J. Am. Soc. Nephrol. 18, 1721 (2007), Abstract;
Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus: F.J. Barrat, et al.; J. Exp. Med. 202, 1131 (2005), Abstract;

General Literature References

DNA motifs suppressing TLR9 responses: A. Trieu; Crit. Rev. Immunol. 26, 527 (2006), Abstract;
Inhibitors of TLR-9 act on multiple cell subsets in mouse and man in vitro and prevent death in vivo from systemic inflammation: O. Duramad, et al.; J. Immunol. 174, 5193 (2005), Abstract;
Inhibitory oligodeoxynucleotides - therapeutic promise for systemic autoimmune diseases?: P. Lenert; Clin. Exp. Immunol. 140, 1 (2005), Abstract;
Suppressive oligodeoxynucleotides protect mice from lethal endotoxic shock: H. Shirota, et al.; J. Immunol. 174, 4579 (2005), Abstract;
Therapeutic potential of oligonucleotides expressing immunosuppressive TTAGGG motifs: D.M. Klinman, et al.; Ann. NY Acad. Sci. 1058, 87 (2005), Abstract;
Immunotherapeutic utility of stimulatory and suppressive oligodeoxynucleotides: K.J. Ishii, et al.; Curr. Opin. Mol. Ther. 6, 166 (2004), Abstract;
Suppressive oligodeoxynucleotides inhibit Th1 differentiation by blocking IFN-gamma- and IL-12-mediated signaling: H. Shirota, et al.; J. Immunol. 173, 5002 (2004), Abstract;
Repetitive elements in mammalian telomeres suppress bacterial DNA-induced immune activation: I. Gursel, et al.; J. Immunol. 171, 1393 (2003), Abstract;

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