Multiple exon skipping compositions for dmd

Abstract

Provided are antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon skipping, and methods of use thereof to treat muscular dystrophy.

1 - 47 . (canceled) 
     
     
         48 . A method of treating muscular dystrophy in a subject, comprising administering to the subject an effective amount of a substantially uncharged antisense compound containing 20-35 morpholino subunits linked by phosphorous-containing intersubunit linkages joining a morpholino nitrogen of one subunit to a 5′ exocyclic carbon of an adjacent subunit, comprising a sequence selected from the group consisting of SEQ ID NOS:1 to 569 and 612 to 635, and capable of forming with the complementary mRNA sequence in a dystrophin-gene exon a heteroduplex structure between said compound and mRNA having a Tm of at least 45° C., wherein the exon is selected from the group consisting of exons 44-55. 
     
     
         49 . The method of  claim 48 , wherein the muscular dystrophy is Duchenne's muscular dystrophy (DMD). 
     
     
         50 . The method of  claim 48 , wherein the muscular dystrophy is Becker muscular dystrophy (BMD). 
     
     
         51 . The method of  claim 48 , wherein the sequence is selected from the group consisting of SEQ ID NOS: 1-20, and the exon is exon 44. 
     
     
         52 . The method of  claim 48 , wherein the sequence is selected from the group consisting of SEQ ID NOS: 21-76 and 612 to 624, and the exon is exon 45. 
     
     
         53 . The method of  claim 48 , wherein the sequence is selected from the group consisting of SEQ ID NOS: 77-125, and the exon is exon 46. 
     
     
         54 . The method of  claim 48 , wherein the sequence is selected from the group consisting of SEQ ID NOS: 126-169, and the exon is exon 47. 
     
     
         55 . The method of  claim 48 , wherein the sequence is selected from the group consisting of SEQ ID NOS: 170-224 and 634, and the exon is exon 48. 
     
     
         56 . The method of  claim 48 , wherein the sequence is selected from the group consisting of SEQ ID NOS: 225-266, and the exon is exon 49. 
     
     
         57 . The method of  claim 48 , wherein the sequence is selected from the group consisting of SEQ ID NOS: 267-308, and the exon is exon 50. 
     
     
         58 . The method of  claim 48 , wherein the sequence is selected from the group consisting of SEQ ID NOS: 309-371, and the exon is exon 51. 
     
     
         59 . The method of  claim 48 , wherein the sequence is selected from the group consisting of SEQ ID NOS: 372-415, and the exon is exon 52. 
     
     
         60 . The method of  claim 48 , wherein the sequence is selected from the group consisting of SEQ ID NOS: 416-475 and 625-633, and the exon is exon 53. 
     
     
         61 . The method of  claim 48 , wherein the sequence is selected from the group consisting of SEQ ID NOS: 476-519, and the exon is exon 54. 
     
     
         62 . The method of  claim 48 , wherein the sequence is selected from the group consisting of SEQ ID NOS: 520-569 and 635, and the exon is exon 55. 
     
     
         63 . The method of  claim 48 , wherein the sequence comprises SEQ ID NO:287. 
     
     
         64 . The method of  claim 48 , wherein the compound is conjugated to an arginine-rich peptide. 
     
     
         65 . The method of  claim 64 , wherein the arginine-rich peptide comprises a sequence is selected from the group consisting of SEQ ID NOS: 570-578.