Aptamer-RNAi therapeutic compositions
A recombinant nucleic acid comprising an aptamer that binds CD4 and an RNAi sequence that silences the expression of RORγ2 is described herein. Pharmaceutical compositions comprising the recombinant nucleic acid, particularly topical compositions are also described. Methods of treating inflammatory disease using the pharmaceutical composition are also described.
1. A recombinant polyribonucleotide comprising a nucleic acid sequence of SEQ ID NO: 1.
2. The recombinant polyribonucleotide of claim 1 wherein the polyribonucleotide is chemically synthesized.
3. The recombinant polyribonucleotide of claim 1 wherein the polyribonucleotide is transcribed from a deoxyribonucleic acid template.
4. The recombinant polyribonucleotide of claim 3 wherein the nucleic acid molecule is transcribed in vitro.
5. The recombinant polyribonucleotide of claim 1 comprising at least one 2′-fluoro ribonucleic acid.
6. The recombinant polyribonucleotide of claim 5 comprising 2′-fluoro cytosine and/or 2′-fluoro uracil.
7. An expression vector comprising:
a first nucleic acid sequence that encodes SEQ ID NO: 1; and
a second nucleic acid sequence comprising a promoter operably linked to the first nucleic acid sequence.
8. The expression vector of claim 7 stably transfected into a cell.
9. A pharmaceutical composition comprising an effective amount of the recombinant polyribonucleotide of claim 1 .
10. The pharmaceutical composition of claim 9 formulated for topical administration.
11. A method of treating a disease mediated by Th17 cells in a subject, the method comprising: administering the pharmaceutical composition of claim 9 to the subject, thereby treating the disease mediated by the Th17 cells.
12. The method of claim 11 wherein the disease comprises rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, psoriasis, inflammatory bowel disease, and type 1 diabetes mellitus.