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 exon 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 exons in a pre-mRNA.

1 - 34 . (canceled) 
     
     
         35 . An antisense oligonucleotide of 15 to 24 nucleotides in length, comprising at least 12 consecutive bases of a base sequence of the sequence CUGUUGCCUCCGGUUCUG (SEQ ID NO: 29), in which uracil bases are thymine bases, wherein the antisense oligonucleotide is a morpholino phosphorodiamidate antisense oligonucleotide, and wherein the antisense oligonucleotide induces exon 53 skipping in the human dystrophin pre-mRNA. 
     
     
         36 . The oligonucleotide of  claim 35 , which is 21 nucleotides in length. 
     
     
         37 . A pharmaceutical composition, comprising the oligonucleotide of  claim 35  and a pharmaceutically acceptable excipient. 
     
     
         38 . A pharmaceutical composition, comprising the oligonucleotide of  claim 36  and a pharmaceutically acceptable excipient. 
     
     
         39 . A method for treating Duchenne Muscular Dystrophy (DMD) or Becker Muscular Dystrophy (BMD), comprising administering to a subject a therapeutically effective amount of the oligonucleotide of  claim 35 . 
     
     
         40 . A method for treating Duchenne Muscular Dystrophy (DMD) or Becker Muscular Dystrophy (BMD), comprising administering to a subject a therapeutically effective amount of the oligonucleotide of  claim 36 .