Immunostimulatory oligonucleotides

Hessel EM, Chu M, Lizcano JO, Chang B, Herman N, Kell SA, Wills-Karp M, Coffman RL Immunostimulatory oligonucleotides block allergic airway inflammation by inhibiting Th2 cell activation and IgE-mediated cytokine induction. J Exp Med 2005 202 1563-1573. 

Smith, J.B. and Wickstrom, E. (1998) Antisense c-myc and immunostimulatory oligonucleotide inhibition of tumorigenesis in a murine B-cell lymphoma transplant model. J. Natl. Cancer Inst., 90, 1146-1154. 

Newer classes of immunostimulatory oligonucleotides that are composed of RNA and bind different receptors are now being identified. Single- and double-stranded RNA have the potential to be proinflammatory, but the receptor and sequence-dependence are distinct from CpG oligonucleotides. These RNA oligonucleotides tend to bind to TLR3, 7, and 8 as well as the... 

Uhlmann E, Vollmer J. Recent advances in the development of immunostimulatory oligonucleotides. Curr Opin Drug Discov Devel. 2003 6 204-217. 

Key words Liposomes, Peptides, DNA, Immunostimulatory oligonucleotides, CpG, Immunization,... 

The immunostimulatory oligonucleotide ODN1668 (5 -TCCATGACG-TTCCTGATGCT-3 ), referred to as CpG was synthesized by Microsynth (Balgach, Switzerland) and stored at -20°C. 

Agrawal S, Kandimalla ER (2001) Antisense and/or immunostimulatory oligonucleotide therapeutics. Curr Cancer Drug Target 1 197-209... 

It has recently been established that bacterial DNA, but not vertebrate DNA, has direct immunostimulatory effects on leukocytes in vitro. The immunostimulatory effect is due to unmethylated CpG dinucleotides, which are underrepresented and methylated in vertebrate DNA. CpG DNA and synthetic oligonucleotides from a variety of sources have shown significant promise as new adjuvants (10-12). CpG induces a strong Thl response, mainly by stimulating cytokine induction and through the expression of costimulatory molecules on antigen-presenting cells. CpG is currently in clinical trials and may become part of a licensed product in the future. 

Pyles, R.B., D. Higgins, C. Chalk, A. Zalar, J. Eiden, C. Brown, G. VanNest, and L.R. Stanberry. 2002. Use of immunostimulatory sequence-containing oligonucleotides as topical therapy for genital herpes simplex virus type 2 infection. J Virol 76 11387. 

Phosphorothioate Oligonucleotides Single-stranded phosphorothioate ODNs (PS ODN), either immunostimulatory or ASO, administered parenter-ally appear rapidly in plasma where they are bound to hydrophilic sites on... 

Immunotoxicity of Oligonucleotide Therapeutics The pro-inflammatory activity of the ASOs produces a constellation of effects, which includes splenomegaly, lymphoid hyperplasia, and multi-organ lymphohistiocytic cell infiltrate driven by the production of pro-inflammatory cytokines [57,63,75]. Incorporation of immunostimulatory sequences like unmethylated CG dinucleotides mimic bacterial DNA [76], Unmethylated CG dinucleotides interact with receptors of the innate immune system such as TLR9 to produce a shift toward T-helper type 1 immunity [77,78], Oligonucleotides with these motifs modulate the immune system. We have recently reported on a direct evaluation for effects on immune function. 

Efficacy of CD8T Cell Induction by Liposomes Containing HCV Epitopes and Influence of an Immunostimulatory CpG Oligonucleotide (21)... 

Uhlmann, E. Vollmer, J. Krieg, A. M. Noll, B. O. CpG immunostimulatory nucleic acids and oligonucleotide analogs for enhancing immune response of vaccines against infection, allergy and cancer. PCX Int. Appl. WO 2005042018, 2005 Chem. Abstr. 2005,142, 462266. 

Yu D, Zhu FG, Bhagat L et al (2002) Potent CpG oligonucleotides containing phosphodiester linkages in vitro and in vivo immunostimulatory properties. Biochem Biophys Res Commun 297 83-90... 

Yu D, Kandimalla ER, Zhao Q et al (2001) Immunostimulatory activity of CpG oligonucleotides containing non-ionic methylphosphonate linkages. Bioorg Med Chem 9 2803-2808... 

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