ODN 4084-F - TLR9 Antagonist

TLR9 Antagonist - Class B inhibitory ODN

Toll-Like Receptor 9 (TLR9) detects unmethylated CpG dinucleotides in bacterial or viral DNA inducing strong immunostimulatory effects.

TLR9 activation can be mimicked by synthetic phosphorothioate-stabilized oligodeoxynucleotides (ODN) containing immune stimulatory “CpG motifs”.

Studies suggest the existence of DNA sequences that can neutralize the stimulatory effect of CpG ODNs.

ODN 4084-F belongs to a new class of inhibitory ODNs [1-2]. It contains an inhibitory DNA motif consisting of two nucleotide triplets, a proximal CCT and a more distal GGG, spaced from each other by four nucleotides.

ODN 4084-F is the shortest active inhibitory ODN. ODN 4084-F is linear and a class B (‘broadly-active') inhibitory ODN. ODN 4084-F is potent inhibitor of TLR9-induced B cells and macrophages [3].

References:

1. Lenert P. et al., 2003. Structural characterization of the inhibitory DNA motif for the type A (D)-CpG-induced cytokine secretion and NK-cell lytic activity in mouse spleen cells. DNA Cell Biol. 22(10):621-31.
2. Lenert PS., 2006. Targeting Toll-like receptor signaling in plasmacytoid dendritic cells and autoreactive B cells as a therapy for lupus.Arthritis Res Ther. 8(1):203.
3. Lenert P. et al., 2009. DNA-like class R inhibitory oligonucleotides (INH-ODNs) preferentially block autoantigen-induced B-cell and dendritic cell activation in vitro and autoantibody production in lupus-prone MRLFas (lpr/lpr) mice in vivo. Arthritis Res Ther. 11(3):R79.