Chimeric immunomodulatory compounds and methods of using the same

1. A method of modulating an immune response in an individual comprising administering to an individual a linear chimeric immunomodulatory compound (CIC) in an amount sufficient to modulate an immune response in said individual, wherein the linear CIC comprises a structure N 1 —S 1 —N 2 —S 2 —N 3 ,

wherein N 1 , N 2 , and N 3 are independently selected nucleic acid moieties comprising 3 to 7 bases, at least one of N 1 , N 2 , and N 3 has the sequence 5′-[(X) 0-2 ]TCG[(X) 2-4 ]-3′, wherein each X is an independently selected nucleotide;

wherein S 1 is a non-nucleic acid spacer moiety covalently bound to N 1 and N 2 ; S 2 is a non-nucleic acid spacer moiety covalently bound to N 2 and N 3 ; S 1 and S 2 are the same or different; each of S 1 and S 2 comprises hexaethylene glycol (HEG), triethyleneglycol (TEG), propyl, butyl, or hexyl; and

wherein said CIC has at least one immunomodulatory activity selected from the group consisting of (i) the ability to stimulate interferon-gamma (IFN-γ) production by human peripheral blood mononuclear cells and (ii) the ability to stimulate interferon-alpha (IFN-α) production by human peripheral blood mononuclear cells.

2. A method of modulating an immune response in an individual comprising administering to an individual a linear CIC in an amount sufficient to modulate an immune response in said individual, wherein the linear CIC is selected from the group consisting of:

5′-TCGTCGA-3′-HEG-5′-ACGTTCG-3′-HEG-5′-AGATGAT-3′

5′-TCGTCG-3′-HEG-5′-ACGTTCG-3′-HEG-5′-AGATGAT-3′

5′-TCGTCGA-3′-HEG-5′-TCGTCGA-3′-HEG-5′-TCGTCGA-3′

5′-TCGTCG-3′-HEG-5′-TCGTCG-3′-HEG-5′-TCGTCG-3′

5′-TCGTCG-3′-HEG-5′-AACGTT-3′-HEG-5′-AGATGAT-3′

5′-TCGTCG-3′-HEG-5′-ACGTTCG-3′-HEG-5′-AGATGAT-3′-

TEG

HEG-5′-TCGTCG-3′-HEG-5′-ACGTTCG-3′-HEG-5′-AGATGAT-

3′-TEG

5′-TCGTTTT-3′-HEG-5′-TCGTTTT-3′-HEG-5′-TCGTTTT-3′

5′-TCGTCGT-3′-HEG-5′-TCGTCGT-3′-HEG-5′-TCGTCGT-3′

5′-TCGAGAT-3′-HEG-5′-TCGAGAT-3′-HEG-5′-TCGAGAT-3′

5′-TCGTCGT-3′-HEG-5′-TGTCGTT-3′-HEG-5′-TGTCGTT-3′

5′-TCGTCGA-3′-HEG-5′-ACGTTCG-3′-HEG-5′-TCGTCGA-3′

5′-TCGTCGA-3′-HEG-5′-ACGTTCG-3′-HEG-5′-GGGGGG-3′

5′-TCGAACG-3′-HEG-5′-TCGAACG-3′-HEG-5′-TCGAACG-3′

5′-TCGACGT-3′-HEG-5′-TCGACGT-3′-HEG-5′-TCGACGT-3′

5′-TCGTCGA-3′-HEG-5′-AACGTTC-3′-HEG-5′-AGATGAT-3′

5′-TCGTCGA-3′-HEG-5′-AACGTTC-3′-HEG-5′-TCGTCGA-3′

5′-TCGTCGA-3′-HEG-5′-AGATGAT-3′-HEG-5′-ACGTTCG-3′

5′-TCGACTC-3′-HEG-5′-TCGAGCG-3′-HEG-5′-TTCTCTT-3′

5′-TCGTCGA-3′-HEG-5′-TCGTCGA-3′-HEG-3′-AGCTGCT-5′

5′-TCGAT-3′-HEG-5′-TCGAT-3′-HEG-5′-TCGAT-3′-HEG-

5′-TCGAT-3′

5′-TCGTCGA-3′-HEG-5′-TCGTCGA-3′-HEG-5′-AACGTTC-3′-

HEG-5′-AGAT-3′

5′-TCGACGT-3′-HEG-5′-TCGACGT-3′-HEG-5′-TCGACGT-3′-

HEG-5′-TCGACGT-3′

5′-TCGATTT-3′-HEG-5′-TCGATTT-3′-HEG-5′-TCGATTT-3′

5′-TCGCTTT-3′-HEG-5′-TCGCTTT-3′-HEG-5′-TCGCTTT-3′

and

5′-TCGGTTT-3′-HEG-5′-TCGGTTT-3′-HEG-5′-TCGGTTT-3′.

3. The method of claim 1 , wherein said modulation comprises an increase in secretion of interferon-gamma (IFN-γ) or interferon-alpha (IFN-α) by blood cells from the individual.

4. The method of claim 1 wherein said modulation is determined by upregulation of immune-associated genes selected from the group consisting of interferon-alpha (IFN-α), interleukin-6 (IL-6), interleukin-12 (IL-12) p40, interferon gamma inducible protein 10 (IP-10) and interleukin-10 (IL-10).

5. The method of claim 1 wherein at least one nucleic acid moiety of the CIC comprises the sequence 5′-TCGACGT-3′ or 5′-TCGTCGA-3′.

6. The method of claim 1 wherein the individual has a disorder selected from the group consisting of asthma, allergy, rhinitis, viral infection, bacterial infection, inflammatory disorder, idiopathic pulmonary fibrosis, and cancer.