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 any one of SEQ ID NO: 141, 142 or 144-188, wherein at least one guanosine base in the sequence is substituted with an inosine base, and wherein said oligonucleotide comprises a modification and induces skipping of exon 53 of human dystrophin pre-mRNA.
2. The oligonucleotide of claim 1 , wherein one to four guanosine bases in the sequence are substituted with an inosine base.
3. The oligonucleotide of claim 1 , wherein the modification is a base and/or sugar modification.
4. The oligonucleotide of claim 3 , wherein the oligonucleotide is a 2′-O-methyl phosphorothioate oligonucleotide.
5. The oligonucleotide of claim 3 , wherein the oligonucleotide is a peptide nucleic acid.
6. The oligonucleotide of claim 3 , wherein the oligonucleotide is a phosphorodiamidate morpholino oligomer.
7. A pharmaceutical composition, comprising the oligonucleotide of claim 1 and a pharmaceutically acceptable carrier.
8. 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 human subject in an amount and for a time which is effective to induce exon skipping.
9. 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 human subject the oligonucleotide of claim 1 .