Oligonucleotide decoys and methods relating thereto

Claim 2

An oligonucleotide for modulating transcription activation of trans-acting factor responsive genes, said oligonucleotide comprising, reading from the 5'-end of said oligonucleotide a first segment, a second segment and a third segment, wherein: (i) said first segment comprises a sequence of deoxynucleotide or nucleotide residues, said sequence comprising a first core recognition sequence having flanking bases on either side; wherein said first segment, when hybridized with the third segment, forms at least one transcription control recognition sequence of at least 6 nucleotides, (ii) said second segment comprises a sequence of deoxynucleotide or nucleotide residues, said sequence having a length sufficient to allow the formation of a first loop structure between the 3'-end of said first segment and the 5'-end of the third segment, and (iii) said third segment comprises a sequence of deoxynucleotide or nucleotide residues, said sequence comprising a second core recognition sequence having flanking bases on either side, and wherein said second core recognition sequence is complementary to said first core recognition sequence.

Claim 3

An oligonucleotide according to claim 1, further comprising a fourth segment, wherein said fourth segment comprises a sequence of deoxynucleotide or nucleotide residues, sufficient to allow the formation of a second loop structure between said first segment and said third segment, wherein said second loop structure is formed by connecting the 5'-end of said first segment to the 3'-end of said fourth segment and the 5'-end of said fourth segment to the 3'-end of said third segment.

Claim 4

An oligonucleotide according to claim 2 wherein there is a break in the oligonucleotide backbone of either the first or third segment thereof.

Claim 5

An oligonucleotide according to claim 3 wherein the oligonucleotide is dephosphorylated at the 5'-end of the break in either the first or third segment.

Claim 6

An oligonucleotide according to claim 4 wherein, in addition to being dephosphorylated, there is deleted from said oligonucleotide, at the site of the break, one or more of said deoxynucleotide or nucleotide residues.

Claim 7

An oligonucleotide according to claim 1 wherein said first and third segments are additionally attached to one another by covalent means of attachment.

Claim 8

An oligonucleotide according to claim 6 wherein said covalent bonds serve to attach the 5'-end of said first segment to the 3'-end of said third segment.

Claim 9

An oligonucleotide according to claim 6 wherein said covalent means of attachment is selected from: a (poly)alkylene bridge, an α,ω-poly(alkylene) dicarboxylic acid, a binuclear Pt II complex selected from: ##STR7## wherein n is 4, 5, or 6; or the result of contacting said oligonucleotide with, psoralen, and then photo-cross-linking by exposure to ultraviolet light.

Claim 10

An oligonucleotide according to claim 1 wherein said sequence of deoxynucleotide or nucleotide residues, sufficient to form a loop structure comprises at least 3 residues.

Claim 11

An oligonucleotide according to claim 1 wherein said oligonucleotide is further modified so as to be capable of forming a covalent bond with a protein which associates with said transcription control recognition sequence.

Claim 12

A composition for modulating transcription activation of trans-acting factor responsive genes, said composition comprising a double-stranded DNA fragment, wherein said DNA fragment contains at least one transcription control recognition sequence of at least 6 nucleotide base pairs, and wherein one strand of said DNA fragment is attached to the other strand by means of at least one linker covalently bound to each strand wherein said linker is selected from: a sequence of bases sufficient to allow the formation of a loop structure between the 3'-end of one strand of said double-stranded DNA fragment and the 5'-end of the strand complementary thereto, or a sequence of bases sufficient to allow the formation of a loop structure between the 5'-end of one strand of said double-stranded DNA fragment and the 3'-end of the strand complementary thereto, or two sequences of bases sufficient to allow the formation of a loop structure between: the 3'-end of the first strand of said double-stranded DNA fragment and the 5'-end of the strand complementary thereto and the 3'-end of the complementary strand of said double-stranded DNA fragment, and the 5'-end of the first strand of said double-stranded DNA fragment.

Claim 13

A composition for modulating transcription activation of trans-acting factor responsive genes, said composition comprising a double-stranded DNA fragment, wherein said DNA fragment contains at least one transcription control recognition sequence of at least 6 nucleotide base pairs, and wherein one strand of said DNA fragment is attached to the other strand by means of at least one linker covalently bound to each strand wherein said linker is selected from: a sequence of bases sufficient to allow the formation of a loop structure between the 3'-end of one strand of said double-stranded DNA fragment and the 5'-end of the strand complementary thereto, or a sequence of bases sufficient to allow the formation of a loop structure between the 5'-end of one strand of said double-stranded DNA fragment and the 3'-end of the strand complementary thereto, or two sequences of bases sufficient to allow the formation of a loop structure between: the 3'-end of the first strand of said double-stranded DNA fragment and the 5'-end of the strand complementary thereto and the 3'-end of the complementary strand of said double-stranded DNA fragment, and the 5'-end of the first strand of said double-stranded DNA fragment.

Claim 14

A composition according to claim 11 wherein one strand of said DNA fragment is additionally covalently bound to the other strand by a covalent linker selected from: a (poly)alkylene bridge, an α,ω-poly(alkylene) dicarboxylic acid, a binuclear Pt II complex selected from: ##STR8## wherein n is 4, 5, or 6; or the result of contacting said oligonucleotide with psoralen, and then photo-cross-linking by exposure to ultraviolet light.

Claim 15

A composition according to claim 11 wherein said sequence of bases sufficient to allow the formation of loop structure(s) comprises in the range of about 3 up to 10 nucleotides.

Claim 16

A composition according to claim 13 wherein said sequence of bases sufficient to allow the formation of loop structure(s) comprises a sequence of any five nucleotide bases.

Claim 17

A method to modulate the transcription of products which are subject to regulation by transcription control recognition sequences, said method comprising administering a therapeutically effective amount of the composition of claim 1 to a subject.

Claim 18

A method to modulate the transcription of products which are subject to regulation by transcription control recognition sequences, said method comprising administering a therapeutically effective amount of the composition of claim 11 to a subject.

Claim 23

A method according to claim 18 wherein said transition metal catalyst is K 2 PtCl 4 .

Claim 24

A method according to claim 18 wherein said oligonucleotide contains at least four or more phosphorothioate diester linkages incorporated into the recognition sequence of the oligonucleotide.