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 . (Cancelled).
37 . A pharmaceutical composition for oral administration comprising
an effective amount of an immunostimulatory nucleic acid of 8 to 100 nucleotides in length, comprising:
5′ X 1 X 2 CGX 3 X 4 3′,
in a pharmaceutically acceptable carrier,
wherein C and G are unmethylated and X 1 , X 2 , X 3 , and X 4 are nucleotides.
38 . The pharmaceutical preparation of claim 37 , wherein the immunostimulatory nucleic acid does not contain a 5′X 1 X 2 CGX 3 X 4 3′ palindrome.
39 . The pharmaceutical composition of claim 37 , wherein the immunostimulatory nucleic acid is 8 to 40 nucleotides in length.
40 . The pharmaceutical composition of claim 37 , wherein the immunostimulatory nucleic acid does not include a GCG trinucleotide at a 5′ and/or 3′ terminal.
41 . The pharmaceutical composition of claim 37 , wherein the immunostimulatory nucleic acid includes a phosphorothioate backbone modification.
42 . The pharmaceutical composition of claim 38 , wherein the immunostimulatory nucleic acid includes a phosphorothioate backbone modification.
43 . The pharmaceutical composition of claim 39 , wherein the immunostimulatory nucleic acid includes a phosphorothioate backbone modification.
44 . The pharmaceutical composition of claim 40 , wherein the immunostimulatory nucleic acid includes a phosphorothioate backbone modification.
45 . The pharmaceutical composition of claim 38 , wherein the immunostimulatory nucleic acid does not include a GCG trinucleotide at a 5′ and/or 3′ terminal.
46 . The pharmaceutical composition of claim 39 , wherein the immunostimulatory nucleic acid does not include a GCG trinucleotide at a 5′ and/or 3′ terminal.
47 . The pharmaceutical composition of claim 45 , wherein the immunostimulatory nucleic acid includes a phosphorothioate backbone modification.
48 . The pharmaceutical composition of claim 46 , wherein the immunostimulatory nucleic acid includes a phosphorothioate backbone modification.
49 . The pharmaceutical composition of claim 37 , wherein the carrier comprises an emulsion.