Minor groove binder (MGB)-oligonucleotide miRNA antagonists

Claim 2

An inhibitor composition for inhibiting non-coding RNAs comprising: an oligonucleotide; and a minor groove binder (MGB), wherein the oligonucleotide comprises nucleotides, wherein all nucleotides of the oligonucleotide comprise ribofuranose having the following structure: wherein Rz is —OCH 3 , and wherein B is a normal base or a modified base, wherein the nucleotides are linked by natural phosphodiester linkages, and wherein the MGB is conjugated to the 5′ end of the oligonucleotide.

Claim 3

The inhibitor composition of claim 1 further comprising a linker through which the MGB is attached to the oligonucleotide.

Claim 4

The inhibitor composition of claim 2 wherein the linker comprises from about 3 to about 100 atoms in a chain selected from the group consisting of C, O. N, S, P. and Si.

Claim 5

The inhibitor composition of claim 2 wherein the linker comprises a trivalent structure, a branched aliphatic chain, a heteroalkyl chain, one or more substituted ring structures, or a combination thereof.

Claim 6

The inhibitor composition of claim 1 wherein the oligonucleotide comprises one or more modified bases.

Claim 7

The inhibitor composition of claim 5 wherein the one or more modified bases comprise 5-propynyluridine, 5-propynylcytidine, 6-methyladenine, 6-methylguanine, N,N,-dimethyladenine, 2-propyladenine, 2-propylguanine, 2-aminoadenine, 1-methylinosine, 3-methyluridine, 5-methylcytidine , 5-methyluridine, 5-(2-amino)propyl uridine, 5-halocytidine, 5-halouridine, 4-acetyleytidine, 1-methyladenosine, 2-methyladenosine, 3-methylcytidine 6-methyluridine, 2-methylguanosine, 7-methylguanosine, 2,2-dimethylguanosine, 5-methylaminoethyluridine, 5-methyloxyuridine, 7-deaza-adenosine, 6-uzeuridine, 6-azocytidine, 6-azothymidine, 5-methyl-2-thiouridine, 2-thiouridine, 4-thiouridine, 2-thiocytidine, dihydrouridine, pseudouridine, queuosine, archaeosine, naphthyl groups, N6-methyladenosine, 5-methylcarbonylmethyluridine, uridine 5-oxyacetic acid, pyridine-4-one, pyridine-2-one, aminophenol, 2,4,6-trimethoxy benzene, 8-substituted adenines and guanines, azapyrimidines, carboxyhydroxyalkyl nucleotides, carboxyalkylaminoai nucleotides, alkylcarbony lalkylated nucleotides, and combinations thereof.

Claim 8

The inhibitor composition of claim 5 , wherein the one or more modified bases comprise one or more bases having 2′ halogen modifications.

Claim 9

The inhibitor composition of claim 1 , wherein the oligonucleotide comprises one or more universal bases.

Claim 10

The inhibitor composition of claim 1 , wherein the oligonucleotide comprises one or more nucleotides having a detectable label.

Claim 11

The inhibitor composition of claim 1 , wherein the oligonucleotide comprises a sequence that is a complement to a mature strand of a target sequence.

Claim 12

The inhibitor composition of claim 1 , wherein the MGB is DPI 3 or CDPI 3 .

Claim 13

The inhibitor composition of claim 1 , wherein the MGB comprises a structure selected from the following group: wherein the subscript m is an integer of from 2 to5; the subscript r is an integer of from 2 to 10; and each R a and R b is independently a linker to the oligonucleotide, a linker to a fluorophore, H, —OR c , —NR c R d , —COOR c or —CONR c R d , wherein each R c and R d is selected from H, (C 2 -C 12 )heteroalkyl (C 3 -C 12 )heteroalkenyl, (C 3 -C 12 )heteroalkynyl, (C 1 -C 12 )alkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, aryl(C 1 -C 12 )alkyl and aryl, wherein one of R a and R b is a linker to the oligonucleotide or to a fluorophore.

Claim 14

The inhibitor composition of claim 12 wherein the rings in the structures contain one or more substitutions selected from H, halogen, (C 1 -C 8 )alkyl, OR g , N(R g ) 2 , N + (R g ) 3 , SR g , COR g , CO 2 R g , CON(R g ) 2 , (CH 2 ) m SO 3 − , (CH 2 ),CO 2 − , (CH 2 ) m OPO 3 −2 , and NHC(O)(CH 2 ) m CO 2 − and esters and salts thereof, wherein each R g is independently H or (C 1 -C 8 )alkyl, and the subscript m is an integer of from 0 to 6.

Claim 15

The inhibitor composition of claim 1 wherein the inhibitor composition comprises one of the following structures: wherein W is a linker having from about 3 to 100 main chain atoms, selected from C, O, N, S, P and Si; [A-B] n is an oligonucleotide wherein A represents a sugar phosphate backbone, modified sugar phosphate backbone, locked nucleic acid backbone, peptidic backbone or a variant thereof used in nucleic acid preparation, wherein W is connected to the 5′ end of [A-B] n , and wherein [A-B] n comprises nucleotides comprising ribofuranose having the following structure: wherein Rz is —OCH 3 , and B is a base, and wherein the nucleotides are linked by natural phosphodiester linkages; n is an integer of from about 3 to about 100; R a , R b , R c , R d , R e and R f are substituents selected from H, halogen, (C 1 -C 8 )alkyl, OR g , N(R g ) 2 , N + (R g ) 3 , SR g , COR g , CO 2 R g CON(R g ) 2 (CH 2 ) m SO 3 − , (CH 2 ) m CO 2 − , (CH 2 ) m OPO 3 −2 , and NHC(O)(CH 2 ) m CO 2 − , and esters and salts thereof, wherein each R g is independently H or (C 1 -C 8 )alkyl, and the subscript m is an integer of from 0 to 6; R h and R w are H or a group having from 1 to 30 atoms selected from C, N, O, P, and S and which is cyclic, acyclic, or a combination thereof.

Claim 16

A method of inhibiting miRNA activity in Nitro or in viNo comprising introducing the inhibitor composition of claim 1 to a location in vitro or in vivo where miRNA activity exists.

Claim 17

A method of treating a condition characterized by over-expression of miRNA comprising administering the inhibitor composition of claim 1 to a subject at a concentration sufficient to inhibit the action of said miRNA.