Methods of producing nucleic acid ligands
AssigneeGilead Sciences, Inc.
InventorsLarry Gold, Craig Tuerk
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Abstract
The present invention includes methods for the identification and production of improved nucleic acid ligands based on the SELEX process. Also included are nucleic acid ligands to the HIV-RT protein identified according to the methods described therein.
Claims56
A method for modifying a nucleic acid ligand for a given target so that the modified ligand has at least one of the following improved properties:
- decreased size;
- improved stability;
- improved binding to the target;
- modification of biological activity of the target;
- resistance to clearance;
- wherein said modifying comprises adding, removing or substituting nucleotide residues, wherein said residues may be chemically modified, and/or chemically modifying said nucleic acid ligand based on:
- (a) determining which nucleotides are crucial to the interaction with the target molecule;
- (b) chemical modification experiments;
- or
- (c) determining the structural conformation of said nucleic acid ligand;
- and
- (d) modifying said ligand based on said determinations made in steps a) through c).
A method for modifying a nucleic acid ligand for a given target, such target being a three dimensional chemical structure other than a polynucleotide that binds to said nucleic acid ligand through a mechanism which predominantly depends on Watson/Crick base pairing, wherein said nucleic acid ligand is not a nucleic acid having the known physiological function of being bound by the target so that the modified ligand has at least one of the following improved properties:
- decreased size;
- improved stability;
- improved binding to the target;
- modification of biological activity of the target;
- capability to cross tissue or cell membrane barriers;
- resistance to clearance;
- wherein said modifying comprises adding, removing or substituting nucleotide residues, wherein said residues may be chemically modified, and/or chemically modifying said nucleic acid ligand based on:
- (a) determining which nucleotides are crucial to the interaction with the target molecule;
- (b) chemical modification experiments;
- or
- (c) determining the structural conformation of said nucleic acid ligand;
- and
- (d) modifying said ligand based on said determinations made in steps a) through c).
The method according to 28 wherein said ligand modifying comprises chemical modification or derivatization of the ligand at the ribose and/or phosphate and/or base positions.
Dependencies are inferred from the claim text.