Combinatorial selection of phosphorothioate single-stranded DNA aptamers for TGF-beta-1 protein
AssigneeBoard of Regents, The University of Texas System
InventorsDavid Gorenstein, Bruce Luxon, Jonghoon Kang, Myung Lee, John Copland
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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.
Claims77
A partially thio-modified aptamer that binds to a TGF-beta protein.
A partially thio-modified aptamer that binds to a TGF-beta receptor.
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.
A partially thio-modified aptamer that binds to a ligand binding trap capable of trapping TGF-beta ligands.
A partially thio-modified aptamer that binds to an auxiliary protein that promotes binding of TGF-beta ligand to Theta signaling receptors.
A partially thio-modified aptamer that binds to a Smad protein.
A partially thio-modified aptamer that binds to a TGF-beta protein complex and enhances TGF-beta activity.
A partially thio-modified aptamer that binds to a TGF-beta protein complex and inhibits TGF-beta activity.
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.
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.
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.
A method of quantitating TGF-β levels in a sample comprising the step of contacting a sample with a TGF-β-specific thioaptamer.
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.
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.
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.
A method of modulating TGF-β signaling comprising the steps of:
- administering to a host a TGF-β3 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.
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.
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.
Dependencies are inferred from the claim text.