Combinatorial selection of phosphorothioate single-stranded DNA aptamers for TGF-beta-1 protein
First Claim
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1. A partially thio-modified aptamer that binds to a TGF-beta protein.
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Abstract
The present invention includes the selection and isolation of thioaptamers that target the signaling protein TGF-β1, compositions of such thioaptamers and the use of such thioaptamers to either block or enhance signal transduction of the TGF-β1 protein and thus function as, e.g., immunomodulatory agents. Thioaptamers may also be targeted alone or in combination with other thioaptamers against the ligand, the receptors, the ligand trap protein(s) and/or the co-receptors to modulate TGF-β signaling pathway.
160 Citations
77 Claims
- 1. A partially thio-modified aptamer that binds to a TGF-beta protein.
- 12. A partially thio-modified aptamer that binds to a TGF-beta receptor.
- 20. A partially thio-modified aptamer that binds to a ligand-receptor complex comprising a TGF-beta ligand and a receptor complex comprising a ThetaRI and a ThetaRII receptors.
- 23. A partially thio-modified aptamer that binds to a ligand binding trap capable of trapping TGF-beta ligands.
- 26. A partially thio-modified aptamer that binds to an auxiliary protein that promotes binding of TGF-beta ligand to Theta signaling receptors.
- 29. A partially thio-modified aptamer that binds to a Smad protein.
- 32. A partially thio-modified aptamer that binds to a TGF-beta protein complex and enhances TGF-beta activity.
- 36. A partially thio-modified aptamer that binds to a TGF-beta protein complex and inhibits TGF-beta activity.
- 39. A partially modified thioaptamer that inhibits TGF-beta activity by binding to a TGF-beta ligand, a TGF-beta ligand-Theta receptor complex, a TGF-beta signaling receptor and co-receptor, to an R-Smad or a Co-Smad.
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41. A partially modified thioaptamer that modifies TGF-beta activity by binding to a TGF-beta ligand, a TGF-beta ligand-Theta receptor complex, a TGF-beta signaling receptor and co-receptor, to an R-Smad or a Co-Smad.
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42. A method of inhibiting TGF-β
- activity comprising the steps of;
providing to a host in need of therapy a pharmaceutically effective amount of a thioaptamer that specifically binds to and inhibits TGF-β
activity. - View Dependent Claims (43)
- activity comprising the steps of;
-
44. A method of quantitating TGF-β
- levels in a sample comprising the step of contacting a sample with a TGF-β
-specific thioaptamer. - View Dependent Claims (45, 46, 47, 48, 49, 50, 51, 52)
- levels in a sample comprising the step of contacting a sample with a TGF-β
-
53. A method of modulating TGF-β
- signaling comprising the steps of;
administering to a host a TGF-β
specific thioaptamer that modulates the activity through the TGF-β
receptor in a dosage effective to reduce activity of the TGF-β
. - View Dependent Claims (54, 55, 56)
- signaling comprising the steps of;
-
57. A method of treating a pathological condition due to increased TGF-β
- activity comprising the steps of;
administering to a host an effective dosage of a thioaptamer that modulates TGF-β
. - View Dependent Claims (58, 59, 60, 61, 62, 63, 64, 65, 66, 67)
- activity comprising the steps of;
-
68. A method of treating a pathological condition in which increased TGF-β
- activity has been implicated comprising the steps of;
administering to a host a TGF-β
specific thioaptamer in a pharmaceutically acceptable carrier at a dosage effective to reduce TGF-β
activity. - View Dependent Claims (69, 70, 71, 72, 73, 74)
- activity has been implicated comprising the steps of;
-
75. A method of modulating TGF-β
- signaling comprising the steps of;
administering to a host a TGF-β
3 ligand binding trap specific thioaptamer that modulates the activity through the TGF-β
receptor in a dosage effective to reduce activity of the TGF-β
.
- signaling comprising the steps of;
-
76. A method of modulating TGF-β
- signaling comprising the steps of;
administering to a host a TGF-β
auxiliary protein specific thioaptamer that modulates the activity through the TGF-β
receptor in a dosage effective to reduce activity of the TGF-β
.
- signaling comprising the steps of;
-
77. A method of modulating TGF-β
- signaling comprising the steps of;
administering to a host a TGF-β
Smad protein specific thioaptamer that modulates the activity through the TGF-β
receptor in a dosage effective to reduce activity of the TGF-β
.
- signaling comprising the steps of;
Specification