Antisense nucleic acids
The present invention provides an oligomer which efficiently enables to cause skipping of the 53rd exon in the human dystrophin gene. Also provided is a pharmaceutical composition which causes skipping of the 53rd exon in the human dystrophin gene with a high efficiency.
1. An antisense oligomer which causes skipping of the 53rd exon in the human dystrophin gene, consisting of the nucleotide sequence of SEQ ID NO: 35, wherein the antisense oligomer is an oligonucleotide having the sugar moiety and/or the phosphate-binding region of at least one nucleotide constituting the oligonucleotide modified, or a morpholino oligomer.
2. The antisense oligomer according to claim 1 , wherein the antisense oligomer is a morpholino oligomer.
3. The antisense oligomer according to claim 1 , wherein the sugar moiety of at least one nucleotide constituting the oligonucleotide is a ribose in which the 2′-OH group is replaced by any one selected from the group consisting of OR, R, R′OR, SH, SR, NH 2 , NHR, NR 2 , N 3 , CN, F, Cl, Br and I (wherein R is an alkyl or an aryl and R′ is an alkylene).
4. The antisense oligomer according to claim 1 , wherein the phosphate-binding region of at least one nucleotide constituting the oligonucleotide is any one selected from the group consisting of a phosphorothioate bond, a phosphorodithioate bond, an alkylphosphonate bond, a phosphoramidate bond and a boranophosphate bond.
5. The antisense oligomer according to claim 2 , wherein the morpholino oligomer is a phosphorodiamidate morpholino oligomer.
6. The antisense oligomer according to claim 2 , wherein the 5 end of the morpholino oligomer is one of the groups of chemical formulae (1) to (3) below:
7. A pharmaceutical composition for the treatment of muscular dystrophy, comprising as an active, ingredient the antisense oligomer according to claim 1 , or a pharmaceutically acceptable salt or hydrate thereof.