Oligonucleotide comprising an inosine for treating DMD
The invention provides an oligonucleotide comprising an inosine, and/or a nucleotide containing a base able to form a wobble base pair or a functional equivalent thereof, wherein the oligonucleotide, or a functional equivalent thereof, comprises a sequence which is complementary to at least part of a dystrophin pre-m RNA exon or at least part of a non-exon region of a dystrophin pre-m RNA said part being a contiguous stretch comprising at least 8 nucleotides. The invention further provides the use of said oligonucleotide for preventing or treating DMD or BMD.
1. An oligonucleotide consisting of the base sequence of SEQ ID NO: 143 provided that each guanosine base may independently be substituted with an inosine base, wherein said oligonucleotide comprises a modification and induces skipping of exon 53 of human dystrophin pre-mRNA.
2. The oligonucleotide of claim 1 , wherein at least one guanosine base is substituted with an inosine base.
3. The oligonucleotide of claim 2 , wherein one to four guanosine bases are substituted with an inosine base.
4. The oligonucleotide of claim 1 , wherein the modification is a base and/or sugar modification.
5. The oligonucleotide of claim 4 , wherein the oligonucleotide is a 2′-O-methyl phosphorothioate oligonucleotide.
6. The oligonucleotide of claim 4 , wherein the oligonucleotide is a peptide nucleic acid oligonucleotide.
7. The oligonucleotide of claim 4 , wherein the oligonucleotide is a phosphorodiamidate morpholino oligomer oligonucleotide.
8. A pharmaceutical composition, comprising the oligonucleotide of claim 1 and a pharmaceutically acceptable carrier.
9. A method for inducing skipping of exon 53 of human dystrophin pre-mRNA in a human subject, comprising administering the oligonucleotide of claim 1 to the subject in an amount and for a time which is effective to induce exon skipping.
10. A method for alleviating one or more symptom(s) of Duchenne Muscular Dystrophy or Becker Muscular Dystrophy in a human subject, comprising administering to the subject the oligonucleotide of claim 1 .