Aptamers as agonists
AssigneeDuke University
InventorsBruce A. Sullenger, James McNamara, Eli Gilboa
Life of this patent
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Abstract
Nucleic acid aptamers are described herein which can transduce a signal into cells by crosslinking a cell surface molecule, thereby inducing of one or more biological activities by the cells; in serving as agonists.
Claims15
A method of identifying a nucleic acid aptamer having agonistic activity (“agonist aptamer”) comprising:
- (a) contacting a nucleic acid aptamer or multimer thereof with cells comprising a ligand to which the nucleic acid aptamer binds;
- and
- (b) detecting a cell activity, which activity is initiated by cell signaling resulting from the binding of the nucleic acid aptamer to the ligand;
- wherein detection of the cell activity is an indication that the nucleic acid aptamer comprises an agonist aptamer.
An agonist aptamer comprising a nucleic acid aptamer made by
- (a) contacting the nucleic acid aptamer, or multimer thereof, with cells comprising a ligand to which the nucleic acid aptamer binds;
- and
- (b) detecting a cell activity, which activity is initiated by a cell signal resulting from the binding of the nucleic acid aptamer to the ligand, the cell activity comprising induction of one or more of cytokine production, apoptosis, cell proliferation, cell differentiation, cell survival, an immune response, and reversal of cell anergy;
- and
- wherein detection of the cell activity is an indication that the nucleic acid aptamer comprises an agonist aptamer.
An isolated nucleic acid aptamer comprising a multimer of at least two molecules of the nucleic acid aptamer joined by a linker comprising a carbon linker;
- wherein the nucleic acid aptamer comprises agonist activity mediated by binding and crosslinking a ligand on cells comprising a ligand for the agonist aptamer.
A method of producing a nucleic acid aptamer having agonistic activity (“agonist aptamer”) comprising:
- (a) contacting a nucleic acid aptamer, or multimer thereof, with cells comprising a ligand to which the nucleic acid aptamer binds;
- wherein the ligand comprises a cell surface molecule expressed by cells comprising T cells;
- and wherein crosslinking of the ligand by the nucleic acid aptamer results in cell signaling;
- and
- (b) detecting a cell activity, which activity is initiated directly or indirectly by cell signaling resulting from the binding of the nucleic acid aptamer to the ligand;
- wherein detection of the cell activity is an indication that the nucleic acid aptamer comprises an agonist aptamer;
- and
- (c) synthesizing the agonist aptamer, in producing agonist aptamer.
An agonist aptamer comprising a nucleic acid aptamer made by
- (a) contacting the nucleic acid aptamer, or multimer thereof, with cells comprising a ligand to which the nucleic acid aptamer binds;
- wherein the ligand comprises a cell surface molecule expressed by cells comprising T cells;
- and wherein crosslinking of the ligand by the nucleic acid aptamer results in cell signaling;
- and
- (b) detecting a cell activity, which activity is initiated by a cell signal resulting from the binding of the nucleic acid aptamer to the ligand, the cell activity comprising induction of one or more of cytokine production, apoptosis, cell proliferation, cell differentiation, cell survival, an immune response, and reversal of cell anergy;
- and
- wherein detection of the cell activity is an indication that the nucleic acid aptamer comprises an agonist aptamer.
Dependencies are inferred from the claim text.