Antisense oligonucleotides for inducing exon skipping and methods of use thereof

Abstract

An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 202.

1 . (canceled) 
     
     
         2 . An isolated antisense oligonucleotide of 20 to 50 nucleotides in length, said oligonucleotide comprising a nucleotide sequence which is complementary to a target sequence of exon 51 of the human dystrophin pre-mRNA, wherein said target sequence comprises a nucleotide sequence that is complementary to the sequence ACA UCA AGG AAG AUG GCA UUU CUA G (SEQ ID NO: 180), and wherein said oligonucleotide comprises a morpholine ring. 
     
     
         3 . An isolated antisense oligonucleotide of 20 to 50 nucleotides in length, said oligonucleotide comprising a nucleotide sequence which is complementary to a target sequence of exon 51 of the human dystrophin pre-mRNA, wherein said target sequence comprises a nucleotide sequence that is complementary to the sequence ACA UCA AGG AAG AUG GCA UUU CUA G (SEQ ID NO: 180), and wherein said oligonucleotide comprises a peptide nucleic acid and/or locked nucleic acid. 
     
     
         4 . An isolated antisense oligonucleotide of 20 to 50 nucleotides in length, said oligonucleotide comprising a nucleotide sequence which is complementary to a target sequence of exon 51 of the human dystrophin pre-mRNA, wherein said target sequence comprises a nucleotide sequence that is complementary to the sequence ACA UCA AGG AAG AUG GCA UUU CUA G (SEQ ID NO: 180), and wherein said oligonucleotide comprises a 2′-O-methyl ribose moiety. 
     
     
         5 . The oligonucleotide of  claim 2 , wherein said oligonucleotide further comprises a phosphorodiamidate internucleoside linkage. 
     
     
         6 . The oligonucleotide of  claim 5 , wherein each linkage is a phosphorodiamidate internucleoside linkage. 
     
     
         7 . The oligonucleotide of  claim 6 , wherein the oligonucleotide is a morpholino phosphorodiamidate oligonucleotide.