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 antisense oligonucleotide of 25 bases comprising a base sequence that is 100% complementary to a target region consisting of 25 consecutive nucleotides of exon 53 of the human dystrophin pre-mRNA, wherein the target region is annealing site H53A(+23+47), annealing site H53A(+39+69), or both, wherein the antisense oligonucleotide base sequence comprises at least 20 consecutive bases of C AUU CAA CUG UUG CCU CCG GUU CUG AAG GUG (SEQ ID NO: 193), wherein uracil bases are thymine bases, wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 53 skipping. 
     
     
         3 . The antisense oligonucleotide of  claim 2 , wherein the antisense oligonucleotide is chemically linked to one or more moieties or conjugates that enhance the activity, cellular distribution, or cellular uptake of the antisense oligonucleotide. 
     
     
         4 . The antisense oligonucleotide of  claim 2 , wherein the oligonucleotide is chemically linked to a polyethylene glycol chain. 
     
     
         5 . A pharmaceutical composition comprising an antisense oligonucleotide of 25 bases comprising a base sequence that is 100% complementary to a target region consisting of 25 consecutive nucleotides of exon 53 of the human dystrophin pre-mRNA, wherein the target region is annealing site H53A(+23+47), annealing site H53A(+39+69), or both, wherein the antisense oligonucleotide base sequence comprises at least 20 consecutive bases of C AUU CAA CUG UUG CCU CCG GUU CUG AAG GUG (SEQ ID NO: 193), wherein uracil bases are thymine bases, wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to the annealing site inducing exon 53 skipping, and a pharmaceutically acceptable carrier. 
     
     
         6 . The pharmaceutical composition of  claim 5 , wherein the antisense oligonucleotide is chemically linked to one or more moieties or conjugates that enhance the activity, cellular distribution, or cellular uptake of the antisense oligonucleotide. 
     
     
         7 . The pharmaceutical composition of  claim 5 , wherein the oligonucleotide is chemically linked to a polyethylene glycol chain.