Claims
- 1. An oligomeric compound comprising a plurality of 2′-hydroxyl ribonucleosides and having a protected phosphate group at the 5′-terminus.
- 2. An oligomeric compound of claim 1 wherein the 5′-terminus phosphate group is protected by a phosphorus protecting group that is stable extracellularly and labile intracellularly.
- 3. An oligomeric compound of claim 2 wherein the lability is due to intracellular esterases.
- 4. An oligomeric compound of claim 2 wherein the lability results in removal of the phosphorus protecting group thereby providing the oligomeric compound having a 5′-phosphate intracellularly.
- 5. An oligomeric compound of claim 1 wherein the phosphorus protecting group is (S-acetyl-2-thioethyl) phosphate (SATE).
- 6. An oligomeric compound of claim 1 wherein the protected phosphate group comprises a 7-methylguanosine residue attached to the 5′-position by a triphosphate linkage to give a reverse orientation.
- 7. An oligomeric compound of claim 6 wherein the 7-methylguanosine residue further comprises an N7 methyl group.
- 8. An oligomeric compound of claim 1 wherein the oligomeric compound is double stranded.
- 9. An oligomeric compound of claim 8 wherein one strand is an antisense strand.
- 10. An oligomeric compound of claim 8 wherein only one strand comprises the protected phosphate group.
- 11. An oligomeric compound of claim 10 wherein one strand is an antisense strand, and wherein the antisense stand comprises the protected phosphate group.
- 12. An oligomeric compound of claim 8 wherein both strands comprise a protected phosphate group.
- 13. An oligomeric compound of claim 1 having the structure:
- 14. An oligomeric compound of claim 13 wherein at least one T3 is F.
- 15. An oligomeric compound of claim 14 wherein at least one T3 is F and at least one T3 is a sugar substituent group.
- 16. An oligomeric compound of claim 15 wherein T2 is hydroxyl.
- 17. An oligomeric compound of claim 15 wherein T2 is a conjugate group.
- 18. An oligomeric compound of claim 13 wherein R1 is H and R2 is a phosphorus protecting group.
- 19. An oligomeric compound of claim 18 wherein R2 is (S-acetyl-2-thioethyl) phosphate (SATE).
- 20. An oligomeric compound of claim 18 wherein R2 is straight or branched C1-C12 alkyl or cyano C1-C12 alkyl.
- 21. An oligomeric compound of claim 18 wherein R2 is cyanoethyl.
- 22. An oligomeric compound of claim 18 wherein R2 is a group of formula:
- 23. An oligomeric compound of claim 18 wherein R is a group of formula:
- 24. An oligomeric compound of claim 23 wherein x is from 1 to about 8.
- 25. An oligomeric compound of claim 24 wherein x is from 1 to 3.
- 26. An oligomeric compound of claim 18 wherein R2 is a group of formula:
- 27. An oligomeric compound of claim 18 wherein R2 is a group of formula:
- 28. An oligomeric compound of claim 18 wherein R2 is a group of formula:
- 29. An oligomeric compound of claim 18 wherein R2 is a group of formula:
- 30. An oligomeric compound of claim 18 wherein R2 is a group of formula:
- 31. An oligomeric compound of claim 30 wherein x is from 1 to about 8.
- 32. An oligomeric compound of claim 30 wherein x is from 1 to 3.
- 33. An oligomeric compound of claim 18 wherein R is a group of formula:
- 34. A method of reducing the expression of a nucleic acid molecule encoding a target comprising contacting the nucleic acid molecule with a compound of claim 1, wherein the compound hybridizes with the nucleic acid molecule encoding the target and reduces the expression of the target.
- 35. A method of screening for a modulator of a target comprising:
contacting a suitable target segment of a nucleic acid molecule encoding the target with one or more candidate modulators of the target; and identifying one or more modulators of the target expression which modulate the expression of the target.
- 36. A method of claim 35 wherein the modulator of the target expression comprises an oligonucleotide, an antisense oligonucleotide, a DNA oligonucleotide, an RNA oligonucleotide, an RNA oligonucleotide having at least a portion of the RNA oligonucleotide capable of hybridizing with RNA to form an oligonucleotide-RNA duplex, or a chimeric oligonucleotide.
- 37. A diagnostic method for identifying a disease state comprising identifying the presence of a target in a sample using at least one primer designed to the target, wherein the primer is a compound of claim 1, and wherein the presence of the target indicates the presence of the disease state.
- 38. A kit or assay device comprising a compound of claim 1.
- 39. A method of treating an animal having a disease or condition associated with a target comprising contacting the animal with a therapeutically or prophylactically effective amount of a compound of claim 1 so that expression of the target is reduced.
- 40. A method of reducing the expression of a gene in a biological system expressing the gene comprising contacting the biological system with a composition comprising a compound of claim 1 under conditions effective to reduce the expression of the gene, wherein the compound comprises at least one RNA strand having at least one modified nucleoside, wherein the modified nucleoside has a phosphate precursor moiety.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. provisional application Serial No. 60/441,433 filed Jan. 16, 2003, which is incorporated herein by reference in its entirety.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60441433 |
Jan 2003 |
US |