EXON SKIPPING COMPOSITIONS FOR TREATING MUSCULAR DYSTROPHY
Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 44 skipping are described.
1 . An antisense oligonucleotide of 20 to 50 bases in length comprising at least 10 consecutive bases of a sequence selected from the group consisting of: SEQ ID NOs: 1-7, wherein the oligonucleotide specifically hybridizes to an exon 44 target region of the human dystrophin pre-mRNA, wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide induces exon 44 skipping, and wherein thymine bases are optionally uracil bases;
or a pharmaceutically acceptable salt thereof.
2 . The antisense oligonucleotide of claim 1 , comprising a base sequence selected from the group consisting of SEQ ID NOs: 1-7.
3 . The antisense oligonucleotide of claim 1 , consisting of a base sequence selected from the group consisting of SEQ ID NOs: 1-7.
4 - 14 . (canceled)
15 . The antisense oligonucleotide of claim 3 , wherein the oligonucleotide is chemically linked to one or more moieties or conjugates that enhance the activity, cellular distribution, or cellular uptake of the antisense oligonucleotide.
16 . (canceled)
17 . The antisense oligonucleotide of claim 15 , wherein the oligonucleotide is chemically linked to a polyethylene glycol moiety.
18 . An antisense oligonucleotide of 20 to 50 bases in length comprising at least 10 consecutive bases of a base sequence complementary to an exon 44 target region of the human dystrophin pre-mRNA designated as an annealing site selected from the group consisting of: H44A(−07+17), H44A(−07+20), H44A(−07+22), H44A(+77+101), H44A(+64+91), H44A(+62+89), and H44A(+62+85), wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide induces exon 44 skipping;
or a pharmaceutically acceptable salt thereof.
19 . The antisense oligonucleotide of claim 18 , wherein the antisense oligonucleotide is 20 to 30 bases in length.
20 . The antisense oligonucleotide of claim 19 , wherein in the base sequence the thymine bases are uracil bases.
21 - 31 . (canceled)
32 . The antisense oligonucleotide of claim 20 , wherein the oligonucleotide is chemically linked to one or more moieties or conjugates that enhance the activity, cellular distribution, or cellular uptake of the antisense oligonucleotide.
33 . (canceled)
34 . The antisense oligonucleotide of claim 32 , wherein the oligonucleotide is chemically linked to a polyethylene glycol moiety.
35 - 37 . (canceled)
38 . A pharmaceutical composition, comprising an antisense oligonucleotide of claim 1 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
39 . A method of treating Duchenne muscular dystrophy in need thereof, comprising administering to the patient an effective amount of a pharmaceutical composition of claim 38 .
40 - 42 . (canceled)
43 . A pharmaceutical composition, comprising an antisense oligonucleotide of claim 18 , or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier.
44 . A method of treating Duchenne muscular dystrophy in a patient in need thereof, comprising administering to the patient an effective amount of a pharmaceutical composition of claim 43 .