Methods of producing nucleic acid ligands
First Claim
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1. 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).
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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.
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Citations
56 Claims
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1. 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:
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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). - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 56)
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28. 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:
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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). - View Dependent Claims (29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55)
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45. 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.
Specification