Reversible platelet inhibition
The present invention relates, in general, to receptors and to platelet aggregation and, in particular, to a method of inhibiting platelet aggregation using an aptamer that binds to and inhibits the activity of a receptor, such as glycoprotein IIb/IIIa (gpIIb/IIIa), and to aptamers suitable for use in such a method. The invention also relates to antidotes to antiplatelet agents and to methods of using such antidotes to reverse aptamer-induced platelet inhibition. The invention further relates to von Willebrand Factor (VWF) inhibitors, and antidotes therefore, and to methods of using same.
1. A nucleic acid aptamer that binds to von Willebrand Factor (VWF) with high affinity and inhibits platelet function in vivo, wherein the aptamer is SEQ ID NO: 56 and includes a 3′ or 5′ modification, wherein said modification confers improved in vivo stability and/or delivery of the nucleic acid aptamer.
2. The aptamer according to claim 1 wherein said aptamer inhibits binding of VWF to GP 1b-IX-V.
3. The nucleic acid aptamer of claim 1 , wherein the modification is selected from a cap, PEG or cholesterol modification.
4. The nucleic acid aptamer of claim 3 , wherein said modification is a 5′ cholesterol modification.
5. A composition comprising said aptamer according to claim 1 and a carrier.
6. A method of inhibiting platelet aggregation in a subject comprising contacting VWF with an amount of said aptamer according to claim 1 so that said inhibition is affected.