METHODS AND MEANS FOR EFFICIENT SKIPPING OF EXON 45 IN DUCHENNE MUSCULAR DYSTROPHY PRE-mRNA

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 said cell with an antisense molecule that binds to a continuous stretch of at least 21 nucleotides within said exon. The invention further relates to such antisense molecule used in said method.

1 - 15 . (canceled) 
     
     
         16 . An antisense oligonucleotide having between 20 and 25 nucleotides which are 100% complementary to 20 to 25 consecutive nucleotides of the human dystrophin pre-mRNA exon 45;
 wherein the antisense oligonucleotide induces exon 45 skipping in the human dystrophin pre-mRNA; and   wherein the antisense oligonucleotide comprises a modification.   
     
     
         17 . The oligonucleotide of  claim 16 , wherein the oligonucleotide has a nucleotide sequence comprising at least 18 consecutive bases of the sequence CGCUGCCCAAUGCCAUCCUGGAGUU (SEQ ID NO: 65), in which uracil bases are thymine bases. 
     
     
         18 . The oligonucleotide of  claim 16 , wherein the modification is a morpholino phosphorodiamidate modification. 
     
     
         19 . A pharmaceutical composition, comprising the oligonucleotide of  claim 16  and a pharmaceutically acceptable excipient. 
     
     
         20 . A method of treating Duchenne Muscular Dystrophy (DMD) or Becker Muscular Dystrophy (BMD), comprising administering to a subject a therapeutically effective amount of the oligonucleotide of  claim 16 .