Nucleic acid modulators of glycoprotein VI

摘要

The present invention relates, in general, to a pharmacologic system to modulate the biology of platelets based upon a nucleic acid ligand that can interact with and modulate the activity of platelet glycoprotein GPVI to regulate platelet function. These nucleic acid ligands are also actively reversible using a modulator that inhibits the activity of the nucleic acid ligand to neutralize this pharmacologic effect and thereby restore GPVI function, including collagen binding, platelet adhesion, collagen-induced platelet activation, and collagen-induced platelet aggregation. The invention further relates to compositions comprising the nucleic acid ligand, the ligand and a modulator, methods to generate the nucleic acid ligand and its modulator, as well as methods of using these agents and compositions in medical therapeutic and diagnostic procedures.

主权项

1. A nucleic acid modulator which binds specifically to a GPVI ligand,
wherein said GPVI ligand is a nucleic acid that comprises a ligand nucleic acid sequence, wherein the ligand nucleic acid sequence is characterized by a secondary structure comprising in a 5′ to 3′ direction a first stem, a first loop, a second stem, a second loop, a third loop, a third stem and a fourth loop; and wherein said fourth loop comprises a consensus sequence comprising UAA.