Modulation of exon recognition in pre-mrna by interfering with the secondary rna structure

Abstract

The invention provides a method for generating an oligonucleotide with which an axon may be skipped in a pre-mRNA and thus excluded from a produced mRNA thereof. Further provided are methods for altering the secondary structure of an mRNA to interfere with splicing processes and uses of the oligonucleotides and methods in the treatment of disease. Further provided are pharmaceutical compositions and methods and means for inducing skipping of several axons in a pre-mRNA.

1 - 34 . (canceled) 
     
     
         35 . An antisense oligonucleotide of 15 to 24 nucleotides in length comprising at least 14 consecutive bases of a base sequence of the sequence GCCCAAUGCCAUCCUGG (SEQ ID NO: 16);
 wherein uracil bases are thymine bases;   wherein the antisense oligonucleotide is a morpholino phosphorodiamidate antisense oligonucleotide; and   wherein the antisense oligonucleotide induces exon 45 skipping in the human dystrophin pre-mRNA.   
     
     
         36 . A method of treating Duchenne Muscular Dystrophy (DMD) or Becker Muscular Dystrophy (BMD), comprising administering to a subject a therapeutically effective amount of the antisense oligonucleotide of  claim 35 . 
     
     
         37 . A pharmaceutical composition, comprising the oligonucleotide of  claim 35  and a pharmaceutically acceptable excipient. 
     
     
         38 . A method of treating Duchenne Muscular Dystrophy (DMD) or Becker Muscular Dystrophy (BMD), comprising administering to a subject a therapeutically effective amount of the pharmaceutical composition of  claim 37 .