G-rich oligo aptamers and methods of modulating an immune response
Aptamer oligonucleotides specifically bind to the DNA binding site of proteins such as Sp1 and Sp1-related proteins which regulate the genes which encode costimulatory molecules such as CD28 and cytokines such as IL-2 and GMCSF. The oligonucleotides compete with the DNA-binding sites of regulatory proteins which specifically regulate molecules to modulate T-cell activation. This serves to modulate gene expression by preventing transcription of the gene. Aptamers are administered to provide therapies for diseases which involve aberrant T-cell activation such as psoriasis, Type I (insulin-dependent) diabetes mellitus, multiple sclerosis, autoimmune uveitis, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease (Crohn's and ulcerative colitis), and septic shock and to regulate normal T-cell activation such as in allograft rejection.
1. An aptamer having a length of no more than 22 nucleotides and having the sequence 5′ GGG GAG GAG GGG CTG GAA 3′ (SEQ ID NO: 5).
2. An aptamer having a length of no more than 22 nucleotides and having the sequence 5′ TTG GAG GGG GAG GAG GGG 3′ (SEQ ID NO: 7).
3. An aptamer having a length of no more than 22 nucleotides and having the sequence 5′ TTG GAG GGG GAG GTG GGG 3′ (SEQ ID NO: 8).
4. A method of treating an isolated immunecompetent cell, comprising administering to the cell an aptamer at a concentration effective to reduce CD28 expression, wherein the aptamer is selected from the group consisting of SEQ ID NO: 5, SEQ ID NO: 7, and SEQ ID NO: 8.
5. The method of claim 4 wherein the immunecompetent cell is from a patient suffering from a graft vs host response.
6. The method of claim 4 wherein the immunecompetent cell is from a patient suffering from an autoimmune disease.
7. The method of claim 6 wherein the autoimmune disease comprises rheumatoid arthritis.
8. The method of claim 6 wherein the autoimmune disease comprises multiple sclerosis.
9. The method of claim 6 wherein the autoimmune disease comprises lupus erythematosus.
10. The method of claim 6 wherein the autoimmune disease comprises insulin dependent diabetes mellitus.
11. The method of claim 6 wherein the autoimmune disease comprises psoriasis.