ANTISENSE OLIGONUCLEOTIDES FOR INDUCING EXON SKIPPING AND METHODS OF USE THEREOF
An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 202.
1 . An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 202.
2 . An antisense molecule according to claim 1 capable of inducing exon skipping in exons 3, 4, 8, 10 to 16, 19 to 40, 42 to 44, 46, 47 and 50 to 53 of the dystrophin gene.
3 . A combination of two or more antisense molecules according to claim 1 or 2 capable of binding to a selected target to induce exon skipping in the dystrophin gene.
4 . A combination or two or more antisense molecules according to claim 3 selected from Table 1B.
5 . A combination of two or more antisense molecules according to claim 1 or 2 joined together to form a “weasel”, wherein said weasel is capable of binding to a selected target to induce exon skipping in the dystrophin gene.
6 . A combination of two or more antisense molecules according to claim 5 selected from Table 1C.
7 . The antisense molecule according to any one of claims 1 to 6 , capable of binding to a selected target site, wherein the target site is an rnRNA splicing site selected from a splicer donor site, splice acceptor sites or exonic splicing enhancer elements.
8 . A method of treating muscular dystrophy in a patient comprising administering to the patient a composition comprising an antisense molecule according to anyone of claims 1 to 6 .
9 . A pharmaceutical or therapeutic composition for the treatment of muscular dystrophy in a patient comprising (a) at least an antisense molecule according to any one of claims 1 to 6 , and (b) one or more pharmaceutically acceptable carriers and/or diluents.
10 . The composition according to claim 9 , comprising about 20 nM to 600 nM of the antisense molecule.
11 . The use of an antisense molecule according to any one of claims 1 to 6 for the manufacture of a medicament for modulation of muscular dystrophy.
12 . An antisense molecule according to any one of claims 1 to 6 for use in antisense molecule based therapy.
13 . An antisense molecule according to any one of claims 1 to 6 as herein before described with reference to the examples.
14 . A kit comprising at least one antisense molecule according to any one of claims 1 to 6 , a suitable carrier and instructions for its use.
15 . An oligomer for ameliorating DMD, the oligomer comprising at least 25 contiguous bases of a base sequence selected from the group consisting of:
a) CXG XXG CCX CCG GXX CXG AAG GXG;
b) C AXX CAA CXG XXG CCX CCG GXX CXG AAG GXG;
and
c) XXG CCX CCG GXX CXG AAG GXG,
wherein X=U or T, wherein the oligomer's base sequence can vary from the above sequence at up to two base positions, and wherein the molecule can bind to a target site to cause exon skipping in an exon of the dystrophin gene.
16 . The oligomer according to claim 15 , wherein the exon of the dystrophin gene at which exon skipping is caused is exon 53.
17 . The oligomer according to claim 15 , wherein the oligomer causes an exon skipping rate of at least 50%.
18 . The oligomer according to claim 15 , wherein the oligomer is between 25 and 35 bases in length.
19 . The oligomer according to claim 15 , wherein the oligomer is 30 bases in length.
20 . The oligomer according to claim 15 , wherein the oligomer is conjugated to or complexed with a distinct chemical entity.
21 . The oligomer according to claim 15 , wherein the oligomer is a phosphorodiamidate morpholino oligonucleotide (PMO).
22 . A vector for ameliorating DMD, the vector encoding an oligomer according to claim 15 , wherein when introduced into a human cell the oligomer is expressed.
23 . A pharmaceutical composition for ameliorating DMD, the composition comprising an oligomer according to claim 15 or a vector according to claim 22 , and a pharmaceutically acceptable carrier, adjuvant or vehicle.
24 . A pharmaceutical composition according to claim 23 comprising a plurality of oligomers or vectors encoding oligomers, or a combination of the oligomers and vectors, wherein the oligomers and/or vectors in the pharmaceutical composition cause skipping in a plurality of exons.