Patent US5786138A successfully refreshed from Google Patents.
US5786138A
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Hyperstabilizing antisense nucleic acid binding agents
Assignee: Louisiana State University
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Filing: 1994-08-11
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Granted: 1998-07-28
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Expires: 2014-08-11
Abstract
Abstract Attaching certain ligands to antisense probes will hyperstabilize sense-antisense duplexes. Such a hyperstabilized duplex is resistant to melting of the strands from one another, to unwinding of the strands, and to the action of nucleases. Applications include antiretroviral action, anti-reverse-transcriptase action, antiviral action, antiparasitical action, antibacterial action, antifungal action, anticancer action, anti-oncogene action, and other applications where it is desired to inhibit gene expression at the genomic or messenger RNA level. The preferred ligands are certain minor-groove-binding agents, exemplified by CC-1065 and synthetic CC-1065 analogs.
Inventors
- 👤 David H. Swenson
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 22:45
CPC Classifications
C; C12; C12N; C12N15/00; C12N15/09; C12N15/11; C12N15/113; C12Q; C12Q1/00; C12Q1/68; C12N2310/00; C12N2310/30; C12N2310/35; C12N2310/351; C12N2310/3511
Claims Analysis
Total Claims: 52
Claim 1
Independent Claim
149 words
A composition for binding a selected ribonucleic acid sequence which is not a homopolymer, comprising: (a) an oligonucleotide which is not a homopolymer, and which is complementary to the selected ribonucleic acid sequence, and which can base-pair to the selected ribonucleic acid sequence to form a double helix having a minor groove and a major groove; and (b) a binding agent which preferentially binds in the minor groove of a double helix formed by the base-pairing of said oligonucleotide and the selected ribonucleic acid sequence, and which increases the strand separation temperature of the double helix; wherein said binding agent is selected from the group consisting of CC-1065, tristabilin, an agent comprising a pyrrolomethoxy hyroxyindole tricyclic ring, U-71,184, an indole, an indole substituted with at least one hydroxy group, an indole substituted with at least one methoxy group, an indole substituted with at least one pyrrole, and a lexitropsin.
Claim 2
Dependent Claim
149 words
A composition for binding a selected ribonucleic acid sequence which is not a homopolymer, comprising: (a) an oligonucleotide which is not a homopolymer, and which is complementary to the selected ribonucleic acid sequence, and which can base-pair to the selected ribonucleic acid sequence to form a double helix having a minor groove and a major groove; and (b) a binding agent which preferentially binds in the minor groove of a double helix formed by the base-pairing of said oligonucleotide and the selected ribonucleic acid sequence, and which increases the strand separation temperature of the double helix; wherein said binding agent is selected from the group consisting of CC-1065, tristabilin, an agent comprising a pyrrolomethoxy hyroxyindole tricyclic ring, U-71,184, an indole, an indole substituted with at least one hydroxy group, an indole substituted with at least one methoxy group, an indole substituted with at least one pyrrole, and a lexitropsin.
Claim 3
Dependent Claim
106 words
A composition for binding a selected ribonucleic acid sequence which is not a homopolymer, comprising: (a) an oligonucleotide which is not a homopolymer, and which is complementary to the selected ribonucleic acid sequence, and which can base-pair to the selected ribonucleic acid sequence to form a double helix having a minor groove and a major groove; and (b) a binding agent which preferentially binds in the minor groove of a double helix formed by the base-pairing of said oligonucleotide and the selected ribonucleic acid sequence, and which increases the strand separation temperature of the double helix, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 4
Dependent Claim
106 words
A composition for binding a selected ribonucleic acid sequence which is not a homopolymer, comprising: (a) an oligonucleotide which is not a homopolymer, and which is complementary to the selected ribonucleic acid sequence, and which can base-pair to the selected ribonucleic acid sequence to form a double helix having a minor groove and a major groove; and (b) a binding agent which preferentially binds in the minor groove of a double helix formed by the base-pairing of said oligonucleotide and the selected ribonucleic acid sequence, and which increases the strand separation temperature of the double helix, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 5
Dependent Claim
13 words
A composition as recited in claim 1, wherein said binding agent comprises CC-1065.
Claim 6
Dependent Claim
17 words
A composition as recited in claim 3, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 7
Dependent Claim
25 words
A composition as recited in claim 4, wherein said binding agent and said oligonucleotide are each covalently bound to succinimidyl 6-(6-(((iodoacetyl) amino) hexanoyl) amino) hexanoate.
Claim 8
Dependent Claim
13 words
A composition as recited in claim 1, wherein said binding agent comprises tristabilin.
Claim 9
Dependent Claim
17 words
A composition as recited in claim 6, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 10
Dependent Claim
16 words
A composition as recited in claim 1, wherein said binding agent comprises a pyrrolomethoxyhydroxyindole tricyclic ring.
Claim 11
Dependent Claim
17 words
A composition as recited in claim 8, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 12
Dependent Claim
16 words
A composition as recited in claim 8, wherein said binding agent comprises three pyrrolomethoxyhydroxyindole tricyclic rings.
Claim 13
Dependent Claim
17 words
A composition as recited in claim 10, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 14
Dependent Claim
16 words
A composition as recited in claim 8, wherein said binding agent comprises two pyrrolomethoxyhydroxyindole tricyclic rings.
Claim 15
Dependent Claim
17 words
A composition as recited in claim 12, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 16
Dependent Claim
16 words
A composition as recited in claim 8, wherein said binding agent comprises four pyrrolomethoxyhydroxyindole tricyclic rings.
Claim 17
Dependent Claim
17 words
A composition as recited in claim 14, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 18
Dependent Claim
13 words
A composition as recited in claim 1, wherein said binding agent comprises U-71,184.
Claim 19
Dependent Claim
17 words
A composition as recited in claim 16, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 20
Dependent Claim
34 words
A composition as recited in claim 1, wherein said binding agent comprises an indole, or an indole substituted with at least one functional group selected from the group consisting of hydroxy, methoxy, and pyrrole.
Claim 21
Dependent Claim
17 words
A composition as recited in claim 18, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 22
Dependent Claim
14 words
A composition as recited in claim 1, wherein said binding agent comprises a lexitropsin.
Claim 23
Dependent Claim
17 words
A composition as recited in claim 20, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 24
Dependent Claim
108 words
A composition for binding a selected ribonucleic acid sequence which is not a homopolymer, comprising: (a) an oligonucleotide which is not a homopolymer, and which is complementary to the selected ribonucleic acid sequence, and which can base-pair to the selected ribonucleic acid sequence to form a double helix having a minor groove and a major groove, wherein said oligonucleotide contains internucleotide bonds which comprise phosphorothioate or methyl phosphonate; and (b) a binding agent which preferentially binds in the minor groove of a double helix formed by the base-pairing of said oligonucleotide and the selected ribonucleic acid sequence, and which increases the strand separation temperature of the double helix.
Claim 25
Dependent Claim
108 words
A composition for binding a selected ribonucleic acid sequence which is not a homopolymer, comprising: (a) an oligonucleotide which is not a homopolymer, and which is complementary to the selected ribonucleic acid sequence, and which can base-pair to the selected ribonucleic acid sequence to form a double helix having a minor groove and a major groove, wherein said oligonucleotide contains internucleotide bonds which comprise phosphorothioate or methyl phosphonate; and (b) a binding agent which preferentially binds in the minor groove of a double helix formed by the base-pairing of said oligonucleotide and the selected ribonucleic acid sequence, and which increases the strand separation temperature of the double helix.
Claim 26
Dependent Claim
17 words
A composition as recited in claim 22, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 27
Dependent Claim
121 words
An in vitro method for binding a selected ribonucleic acid sequence which is not a homopolymer, comprising the steps of: (a) contacting the selected ribonucleic acid sequence in vitro with an oligonucleotide which is not a homopolymer, and which is complementary to the selected ribonucleic acid sequence, and which can base-pair to the selected ribonucleic acid sequence to form a double helix having a minor groove and a major groove, until such a double helix is formed; and (b) contacting the double helix in vitro with a binding agent which preferentially binds in the minor groove of the double helix, and which increases the strand separation temperature of the double helix, until said binding agent has bound in the minor groove.
Claim 28
Dependent Claim
121 words
An in vitro method for binding a selected ribonucleic acid sequence which is not a homopolymer, comprising the steps of: (a) contacting the selected ribonucleic acid sequence in vitro with an oligonucleotide which is not a homopolymer, and which is complementary to the selected ribonucleic acid sequence, and which can base-pair to the selected ribonucleic acid sequence to form a double helix having a minor groove and a major groove, until such a double helix is formed; and (b) contacting the double helix in vitro with a binding agent which preferentially binds in the minor groove of the double helix, and which increases the strand separation temperature of the double helix, until said binding agent has bound in the minor groove.
Claim 29
Dependent Claim
17 words
A method as recited in claim 24, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 30
Dependent Claim
13 words
A method as recited in claim 24, wherein said binding agent comprises CC-1065.
Claim 31
Dependent Claim
17 words
A method as recited in claim 26, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 32
Dependent Claim
25 words
A method as recited in claim 27, wherein said binding agent and said oligonucleotide are each covalently bound to succinimidyl 6-(6-(((iodoacetyl) amino) hexanoyl) amino) hexanoate.
Claim 33
Dependent Claim
13 words
A method as recited in claim 24, wherein said binding agent comprises tristabilin.
Claim 34
Dependent Claim
17 words
A method as recited in claim 29, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 35
Dependent Claim
16 words
A method as recited in claim 30, wherein said binding agent comprises a pyrrolomethoxyhydroxyindole tricyclic ring.
Claim 36
Dependent Claim
17 words
A method as recited in claim 31, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 37
Dependent Claim
16 words
A method as recited in claim 31, wherein said binding agent comprises three pyrrolomethoxyhydroxyindole tricyclic rings.
Claim 38
Dependent Claim
17 words
A method as recited in claim 33, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 39
Dependent Claim
16 words
A method as recited in claim 31, wherein said binding agent comprises two pyrrolomethoxyhydroxyindole tricyclic rings.
Claim 40
Dependent Claim
17 words
A method as recited in claim 35, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 41
Dependent Claim
16 words
A method as recited in claim 31, wherein said binding agent comprises four pyrrolomethoxyhydroxyindole tricyclic rings.
Claim 42
Dependent Claim
17 words
A method as recited in claim 37, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 43
Dependent Claim
13 words
A method as recited in claim 24, wherein said binding agent comprises U-71,184.
Claim 44
Dependent Claim
17 words
A method as recited in claim 39, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 45
Dependent Claim
34 words
A method as recited in claim 24, wherein said binding agent comprises an indole, or an indole substituted with at least one functional group selected from the group consisting of hydroxy, methoxy, and pyrrole.
Claim 46
Dependent Claim
17 words
A method as recited in claim 41, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 47
Dependent Claim
14 words
A method as recited in claim 24, wherein said binding agent comprises a lexitropsin.
Claim 48
Dependent Claim
17 words
A method as recited in claim 43, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 49
Dependent Claim
19 words
A method as recited in claim 24, wherein said oligonucleotide contains internucleotide bonds which comprise phosphorothioate or methyl phosphonate.
Claim 50
Dependent Claim
17 words
A method as recited in claim 45, wherein said binding agent is chemically tethered to said oligonucleotide.
Claim 51
Dependent Claim
6 words
A composition of matter comprising tristabilin.
Claim 52
Dependent Claim
6 words
A composition of matter comprising tristabilin.
References Cited (Backward Citations)
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