METHODS AND MEANS FOR EFFICIENT SKIPPING OF EXON 45 IN DUCHENNE MUSCULAR DYSTROPHY PRE-mRNA
First Claim
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1. An isolated antisense oligonucleotide consisting of 22, 23, 24, 25, 26, 27, 28 or 29 nucleotides, wherein said oligonucleotide is complementary along its entire length to a sequence in part of the human dystrophin exon 45 pre-mRNA, wherein said sequence is complementary to at least 22 nucleotides of a sequence consisting of 5′
- -UUUGCCGCUGCCCAAUGCCAUCCUG-3′
(SEQ ID NO;
3).
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Abstract
The invention relates to a method for inducing or promoting skipping of exon 45 of DMD pre-mRNA in a Duchenne Muscular Dystrophy patient, preferably in an isolated (muscle) cell, the method comprising providing an isolate muscle cell with a molecule that binds to a continuous stretch of at least 21 nucleotides within said exon. The invention further relates to such molecule used in the method.
50 Citations
47 Claims
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1. An isolated antisense oligonucleotide consisting of 22, 23, 24, 25, 26, 27, 28 or 29 nucleotides, wherein said oligonucleotide is complementary along its entire length to a sequence in part of the human dystrophin exon 45 pre-mRNA, wherein said sequence is complementary to at least 22 nucleotides of a sequence consisting of 5′
- -UUUGCCGCUGCCCAAUGCCAUCCUG-3′
(SEQ ID NO;
3). - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 15, 16, 18, 19, 20, 21, 22, 28, 30, 41, 42, 43)
- -UUUGCCGCUGCCCAAUGCCAUCCUG-3′
-
13. An isolated antisense oligonucleotide consisting of 22, 23, 24, 25, 26, 27, 28, or 29 nucleotides, wherein said oligonucleotide is complementary along its entire length to a sequence in part of the human dystrophin exon 45 pre-mRNA, wherein said sequence is complementary to at least 22 nucleotides of a sequence consisting of 5′
- UUUGCCGCUGCCCAAUGCCAUCCUG 3′
(SEQ ID NO;
3);
wherein each sugar moiety of the oligonucleotide is 2′
-O-methyl substituted and each of the internucleoside linkages present in the oligonucleotide comprises a phosphorothioate moiety. - View Dependent Claims (17, 23, 24, 25, 26, 27, 29)
- UUUGCCGCUGCCCAAUGCCAUCCUG 3′
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31. An oligomer for ameliorating DMD, the oligomer consisting of 22, 23, 24, 25, 26, 27, 28, or 29 nucleotides, comprising at least 22 nucleotides of the base sequence of 5′
- -UUUGCCGCUGCCCAAUGCCAUCCUG-3′
(SEQ ID;
NO;
3);
wherein the bases of the oligomer are selected from the group consisting of;
adenine, cytosine, guanine, thymine and uracil; and
wherein the molecule can bind to a target site to cause exon skipping in an exon of the dystrophin gene. - View Dependent Claims (32, 33, 34)
- -UUUGCCGCUGCCCAAUGCCAUCCUG-3′
-
35. An oligomer for alleviating DMD, the oligomer consisting of 25 nucleotides, and consisting of the sequence 5′
- -UUUGCCGCUGCCCAAUGCCAUCCUG-3′
(SEQ ID;
NO;
3);
wherein the molecule can bind to a target site to cause exon skipping in an exon of the dystrophin gene.
- -UUUGCCGCUGCCCAAUGCCAUCCUG-3′
-
36. An isolated antisense oligomer whose base sequence consists of the base sequence of 5′
- -UUUGCCGCUGCCCAAUGCCAUCCUG-3′
(SEQ ID;
NO;
3).
- -UUUGCCGCUGCCCAAUGCCAUCCUG-3′
-
37. An isolated antisense oligomer consisting of 22, 23, 24, 25, 26, 27, 28, or 29 nucleotides comprising at least 22 nucleotides of the base sequence of 5′
- -UUUGCCGCUGCCCAAUGCCAUCCUG-3′
(SEQ ID;
NO;
3). - View Dependent Claims (38, 39, 40)
- -UUUGCCGCUGCCCAAUGCCAUCCUG-3′
-
44. An isolated antisense oligonucleotide consisting of 22, 23, 24, 25, 26, 27, 28, or 29 nucleotides, wherein said oligonucleotide is complementary to at least 22 nucleotides of a sequence consisting of 5′
- UUUGCCGCUGCCCAAUGCCAUCCUG 3′
(SEQ ID NO;
3).
- UUUGCCGCUGCCCAAUGCCAUCCUG 3′
-
45. An isolated antisense oligonucleotide, consisting of 22, 23, 24, 25, 26, 27, 28 or 29 nucleotides, wherein said oligonucleotide is complementary to at least 22 nucleotides of a sequence consisting of 5′
- UUUGCCGCUGCCCAAUGCCAUCCUG 3′
(SEQ ID NO;
3);
wherein said oligonucleotide comprises at least one 2′
-O-methyl substituted sugar moiety and at least one internucleoside linkage. - View Dependent Claims (46, 47)
- UUUGCCGCUGCCCAAUGCCAUCCUG 3′
Specification