Compositions and methods for modulation of smn2 splicing

Abstract

Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a cell, tissue or animal. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.

What is claimed is: 
     
         1 - 23 . (canceled) 
     
     
         24 . An antisense oligonucleotide targeted to exon 7 of a nucleic acid molecule encoding SMN2, wherein said oligonucleotide is 12 to 20 nucleotides in length and comprises a 2′-O-methoxyethyl sugar modification at each position. 
     
     
         25 . The oligonucleotide of  claim 24  which is 12 nucleotides in length. 
     
     
         26 . The oligonucleotide of  claim 24  which is 15 nucleotides in length. 
     
     
         27 . The oligonucleotide of  claim 24  which is 18 nucleotides in length. 
     
     
         28 . The oligonucleotide of  claim 24  which is targeted to exon 7. 
     
     
         29 . The oligonucleotide of  claim 28  wherein the target site of said oligonucleotide is nucleotide 64, 65, 66, 67, 68, 94, 95, 96 or 97 of SEQ ID NO: 1. 
     
     
         30 . The oligonucleotide of  claim 28 , wherein the nucleotide sequence of said oligonucleotide comprises at least an 8-nucleobase portion of SEQ ID NO: 37, 38, 41, 59, 62, 63, 64, 66, 67 or 68. 
     
     
         31 . The oligonucleotide of  claim 28 , wherein the nucleotide sequence of said oligonucleotide comprises at least an 10-nucleobase portion of SEQ ID NO: 37, 38, 41, 59, 62, 63, 64, 66, 67 or 68. 
     
     
         32 . The oligonucleotide of  claim 28 , wherein the nucleotide sequence of said oligonucleotide comprises at least an 12-nucleobase portion of SEQ ID NO: 37, 38, 41, 59, 62, 63, 64, 66, 67 or 68. 
     
     
         33 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 24 .