Claims
- 1. An oligoribonucleotide of from 21 to 30 nucleotides comprising:
a contiguous sequence of SEQ ID NO:1 or a sequence which has one-base mismatch with SEQ ID NO:1, wherein the ribose residue of at least one nucleotide is protected at the 2′-O-position by 2,4-dinitrophenyl (DNP) and wherein the oligoribonucleotide is capable of down-regulating the expression of the Rlα subunit of protein kinase A.
- 2. The oligoribonucleotide of claim 1 wherein the oligoribonucleotide has from 21 to 25 nucleotides.
- 3. The oligoribonucleotide of claim 2, wherein the oligoribonucleotide has from 21-23 nucleotides.
- 4 The oligoribonucleotide of claim 3, wherein the oligoribonucleotide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19 and SEQ ID NO:22.
- 5. The oligoribonucleotide of claim 4, wherein the oligoribonucleotide is SEQ ID NO:1.
- 6. The oligoribonucleotide of claim 1, wherein the one-base mismatch is selected from the group consisting of SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18 and SEQ ID NO:19.
- 7. The oligoribonucleotide of claim 1, wherein the DNP to nucleotide molar ratio is between 0.5 to 0.8
- 8. The oligoribonucleotide of claim 7, wherein the DNP to nucleotide molar ratio is between 0.65 to 0.75.
- 9. A composition comprising the oligoribonucleotide of claim 1.
- 10. The composition of claim 9, further a comprising a complementary strand to the oligoribonucleotide.
- 11. The composition of claim 9 further comprising a pharmaceutically acceptable carrier.
- 12 The composition of claim 11, further comprising a chemotherapeutic agent.
- 13. The composition of claim 9, wherein the oligoribonucleotide has a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO :19, SEQ ID NO:22 and combinations thereof.
- 14. The composition of claim 13, wherein the oligoribonucleotide has the sequence of SEQ ID NO:1.
- 15. A method of down regulating the expression of RIα/PKA gene in a cell comprising providing to the cell the oligoribonucleotide of claim 1 in an amount effective to down-regulate the expression of the RIα/PKA gene.
- 16. The method of claim 15, wherein the sequence of the oligoribonucleotide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:I0, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:22 and combinations thereof.
- 17. The method of claim 16, wherein the sequence of the oligoribonucleotide is SEQ ID NO:1.
- 18. A method of reducing the growth of cells which overexpress the RIα/PKA gene comprising providing to the cells a composition comprising the oligoribonucleotide of claim 1 in an amount effective to reduce the growth of the cells.
- 19. The method of claim 18, wherein the sequence of the oligoribonucleotide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18 , SEQ ID NO:19 and SEQ ID NO:22.
- 20. The method of claim 19, wherein the sequence of the oligoribonucleotide is SEQ ID NO:1.
- 21. A method of reducing the growth of cancer cells in an individual comprising administering to the individual a growth inhibiting regimen of the composition of claim 9.
- 22. The method of claim 21, wherein the sequence of the oligoribonucleotide in the composition is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:22 and combinations thereof.
- 23. The method of claim 22, wherein the sequence of the oligoribonucleotide is SEQ ID NO:1.
- 24. The method of claim 21, wherein the administration of the composition is combined with a treatment selected from the group consisting of surgery, radiation, chemotherapy and immunotherapy.
- 25. The method of claim 21, wherein the composition is administered via a route selected from the group consisting of intratumoral, intravenous, intraperitoneal, intramuscular, intranasal, oral, topical and rectal.
- 26. A method for detecting the overexpression of the RIα/PKA gene in a test sample comprising the steps of:
a) isolating nucleic acids from the test sample and a control sample; b) contacting the nucleic acids from the test sample and the control sample with the oligoribonucleotide of claim 1 or a complement thereof; and c) comparing hybridization of the nucleic acids from the test and the control sample to the oligoribonucleotide of claim 1 or the complement thereof, wherein an increase in the hybridization in the test sample is indicative of the overexpression of the RIα/PKA gene is the test sample.
- 27. The method of claim 26, wherein the nucleic acids are mRNA.
- 28. The method of claim 26, wherein the nucleic acids are reverse transcribed from mRNA.
- 30. The method of claim 26, wherein the oligoribonucleotide is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:10, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19 and SEQ ID NO:22.
- 31. The method of claim 30, wherein the oligonucleotide has a sequence of SEQ ID NO:1.
- 32. An oligoribonucleotide of from 18 to 30 nucleotides comprising:
a contiguous sequence of SEQ ID NO:20 or a sequence which has one-base mismatch with SEQ ID NO:20, wherein the ribose residue of at least one nucleotide is protected at the 2′-O-position by 2,4-dinitrophenyl (DNP) and wherein the oligoribonucleotide is capable of down-regulating the expression of the RIα subunit of protein kinase A.
- 33. The oligoribonucleotide of claim 32, which has a sequence of SEQ ID NO:20.
- 34. A composition comprising the oligoribonucleotide of claim 32.
Parent Case Info
[0001] This application claims priority to U.S. Provisional Application No. 60/431,594, filed on Dec. 5, 2003, the disclosure of which is incorporated herein by reference.
Provisional Applications (1)
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Number |
Date |
Country |
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60431594 |
Dec 2002 |
US |