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

摘要

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.

主权项

1. 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:(SEQ ID NO: 2)5′-AGAUAGUCUACAACAAAGCUCAGGUCGGAUUGACAUUAUUCAUAGCAAGAAGACAGCAGCAUUGCAAAGUGCAACGCCUGUGG-3′, andwherein said oligonucleotide is capable ofskipping exon 43;(SEQ ID NO: 3)5′-UUAUGGUUGGAGGAAGCAGAUAACAUUGCUAGUAUCCCACUUGAACCUGGAAAAGAGCAGCAACUAAAAGAAAAGC-3′, andwherein said oligonucleotide is capable ofskipping exon 46;(SEQ ID NO: 4)5′-GCGGTAAACCGUUUACUUCAAGAGCUGAGGGCAAAGCAGCCUGACCUAGCUCCUGGACUGACCACUAUUGG-3′, and whereinsaid oligonucleotide is capable of skipping exon50;(SEQ ID NO: 5)5′-CUCCUACUCAGACUGUUACUCUGGUGACACAACCUGUGGUUACUAAGGAAACUGCCAUCUCCAAACUAGAAAUGCCAUCUUCCUUGAUGUUGGAGGUAC-3′, and wherein said oligonucleotide iscapable of skipping exon 51;(SEQ ID NO: 6)5′-AUGCAGGAUUUGGAACAGAGGCGUCCCCAGUUGGAAGAACUCAUUACCGCUGCCCAAAAUUUGAAAAACAAGACCAGCAAUCAAGAGGCU-3′, and wherein said oligonucleotide is capable ofskipping exon 52,and(SEQ ID NO: 7)5′-AAUGUUAAAGGAUUCAACACAAUGGCUGGAAGCUAAGGAAAAGCUGAGCAGGUCUUAGGACAGGCCAGAG-3′, and whereinsaid oligonucleotide is capable of skipping exon53.