Immunomodulatory oligonucleotides
Oligonucleotides containing unthylated CpG dinucleotides and therapeutic utilities based on their ability to stimulate an immune response in a subject are disclosed. Also disclosed are therapies for treating diseases associated with immune system activation that are initiated by unthylated CpG dinucleotides in a subject comprising administering to the subject oligonucleotides that do not contain unmethylated CpG sequences (i.e. methylated CpG sequences or no CpG sequence) to outcompete unmethylated CpG nucleic acids for binding. Further disclosed are methylated CpG containing dinucleotides for use antisense therapies or as in vivo hybridization probes, and immunoinhibitory oligonucleotides for use as antiviral therapeutics.
1 - 36 . (canceled)
37 . A composition comprising:
an immunostimulatory oligonucleotide of 8 to 40 nucleotides in length, comprising:
5′X 1 X 2 CGX 3 X 4 3′, wherein C and G are unmethylated and X 1 , X 2 , X 3 , and X 4 are nucleotides, and
an antigen in a pharmaceutically acceptable carrier, wherein the composition is a vaccine.
38 . The composition of claim 37 , wherein the immunostimulatory oligonucleotide does not include a GCG trinucleotide at a 5′ and/or 3′ terminal.
39 . The composition of claim 37 , wherein the immunostimulatory oligonucleotide does not contain a 5′X 1 X 2 CGX 3 X 4 3′ palindrome.
40 . The composition of claim 38 , wherein the immunostimulatory oligonucleotide does not contain a 5′X 1 X 2 CGX 3 X 4 3′ palindrome.
41 . The composition of claim 37 , wherein the immunostimulatory oligonucleotide includes a phosphorothioate backbone modification.
42 . The composition of claim 38 , wherein the immunostimulatory oligonucleotide includes a phosphorothioate backbone modification.
43 . The composition of claim 39 , wherein the immunostimulatory oligonucleotide includes a phosphorothioate backbone modification.
44 . The composition of claim 40 , wherein the immunostimulatory oligonucleotide includes a phosphorothioate backbone modification.
45 . A method of inducing an antigen-specific immune response in a subject comprising: administering the vaccine of claim 37 to a subject, in an amount effective to induce the antigen-specific immune response.
46 . A method of inducing an antigen-specific immune response in a subject comprising: administering the vaccine of claim 38 to a subject, in an amount effective to induce the antigen-specific immune response.
47 . A method of inducing an antigen-specific immune response in a subject comprising: administering the vaccine of claim 39 to a subject, in an amount effective to induce the antigen-specific immune response.
48 . A method of inducing an antigen-specific immune response in a subject comprising: administering the vaccine of claim 40 to a subject, in an amount effective to induce the antigen-specific immune response.
49 . A method of inducing an antigen-specific immune response in a subject comprising: administering the vaccine of claim 41 to a subject, in an amount effective to induce the antigen-specific immune response.
50 . A method of inducing an antigen-specific immune response in a subject comprising: administering the vaccine of claim 42 to a subject, in an amount effective to induce the antigen-specific immune response.
51 . A method of inducing an antigen-specific immune response in a subject comprising: administering the vaccine of claim 43 to a subject, in an amount effective to induce the antigen-specific immune response.
52 . A method of inducing an antigen-specific immune response in a subject comprising: administering the vaccine of claim 44 to a subject, in an amount effective to induce the antigen-specific immune response.