Methods and means for efficient skipping of at least one of the following exons of the human duchenne muscular dystrophy gene: 43, 46, 50-53
AssigneesBioMarin Technologies B.V., Academisch Ziekenhuis Leiden
InventorJudith Christina Theodora Van Deutekom
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Abstract
The invention relates a method wherein a molecule is used for inducing and/or promoting skipping of at least one of exon 43, exon 46, exons 50-53 of the DMD pre-mRNA in a patient, preferably in an isolated cell of a patient, the method comprising providing said cell and/or said patient with a molecule. The invention also relates to said molecule as such.
Claims20
An isolated antisense oligonucleotide which is fully complementary to 8-22 consecutive nucleotides of a sequence of an exon of human dystrophin pre-mRNA, said oligonucleotide comprising a locked nucleic acid, wherein said sequence of said exon is selected from the group consisting of:
- 5′-AGAUAGUCUACAACAAAGCUCAGGUCGGAUUGACAUUAUUCAUAG CAAGAAGACAGCAGCAUUGCAAAGUGCAACGCCUGUGG-3′ (SEQ ID NO:
- 2), and wherein said oligonucleotide is capable of skipping exon 43;
- 5′-UUAUGGUUGGAGGAAGCAGAUAACAUUGCUAGUAUCCCACUUGAA CCUGGAAAAGAGCAGCAACUAAAAGAAAAGC-3′ (SEQ ID NO:
- 3), and wherein said oligonucleotide is capable of skipping exon 46;
- 5′-GCGGTAAACCGUUUACUUCAAGAGCUGAGGGCAAAGCAGCCUGAC CUAGCUCCUGGACUGACCACUAUUGG-3′ (SEQ ID NO:
- 4), and wherein said oligonucleotide is capable of skipping exon 50;
- 5′-CUCCUACUCAGACUGUUACUCUGGUGACACAACCUGUGGUUACUA AGGAAACUGCCAUCUCCAAACUAGAAAUGCCAUCUUCCUUGAUG UUGGAGGUAC-3′ (SEQ ID NO:
- 5), and wherein said oligonucleotide is capable of skipping exon 51;
- 5′-AUGCAGGAUUUGGAACAGAGGCGUCCCCAGUUGGAAGAACUCAUU ACCGCUGCCCAAAAUUUGAAAAACAAGACCAGCAAUCAAGAGGCU-3′ (SEQ ID NO:6), and wherein said oligonucleotide is capable of skipping exon 52, and
- 5′-AAUGUUAAAGGAUUCAACACAAUGGCUGGAAGCUAAGGAAAAGCU GAGCAGGUCUUAGGACAGGCCAGAG-3′ (SEQ ID NO:7), and wherein
- said oligonucleotide is capable of skipping exon 53.
A method for treating one or more symptom(s) of Duchenne Muscular Dystrophy or Becker Muscular Dystrophy in an individual, the method comprising administering to said individual a pharmaceutical composition of claim 15, wherein said composition induces skipping of exons of dystrophin pre-mRNA.
Dependencies are inferred from the claim text.