Method for efficient exon (44) skipping in duchenne muscular dystrophy and associated means

Abstract

The invention relates to a nucleic acid molecule that binds and/or is complementary to the nucleotide molecule having sequence 5′-GUGGCUAACAGAAGCU (SEQ ID NO:1), 5′-GGGAACAUGCUAAAUAC (SEQ ID NO:2), 5′-AGACACAAAUUCCUGAGA (SEQ ID NO:3), or 5′-CUGUUGAGAAA (SEQ ID NO. 4), and to its use in a method for inducing skipping of exon 44 of the DMD gene in a DMD patient.

1 . (canceled) 
     
     
         2 . An oligonucleotide 16 to 25 nucleotides in length that comprises a base sequence selected from SEQ ID NOS: 35-40 and 42-45, wherein the oligonucleotide induces skipping of exon 44 of human dystrophin pre-mRNA and comprises a modification. 
     
     
         3 . The oligonucleotide of  claim 2 , which is a 2′-O-alkyl phosphorothioate oligonucleotide. 
     
     
         4 . The oligonucleotide of  claim 3 , which is a 2′-O-methyl phosphorothioate oligonucleotide. 
     
     
         5 . The oligonucleotide of  claim 2 , wherein the modification comprises a modified backbone. 
     
     
         6 . The oligonucleotide of  claim 5 , wherein the modified backbone is selected from the group consisting of a morpholino backbone, a carbamate backbone, a siloxane backbone, a sulfide backbone, a sulfoxide backbone, a sulfone backbone, a formacetyl backbone, a thioformacetyl backbone, a methyleneformacetyl backbone, a riboacetyl backbone, an alkene containing backbone, a sulfamate backbone, a sulfonate backbone, a sulfonamide backbone, a methyleneimino backbone, a methylenehydrazino backbone and an amide backbone. 
     
     
         7 . The oligonucleotide of  claim 2 , wherein the modification is selected from the group consisting of: phosphorodiamidate morpholino oligomer (PMO), peptide nucleic acid, and locked nucleic acid. 
     
     
         8 . The oligonucleotide of  claim 7 , wherein the modification is PMO. 
     
     
         9 . A pharmaceutical composition, comprising the oligonucleotide of  claim 2  and a pharmaceutically acceptable carrier. 
     
     
         10 . A method of treating Duchenne muscular dystrophy or Becker muscular dystrophy in a subject, comprising administering to the subject the oligonucleotide of  claim 2 .