Exon skipping compositions for treating muscular dystrophy
Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 44 skipping are described.
1. An antisense oligonucleotide of 28 bases comprising the base sequence of SEQ ID NO: 6, in which thymine bases are optionally uracil bases;
wherein the sugar moieties of the oligonucleotide backbone are replaced with morpholinos; and
wherein the antisense oligonucleotide is conjugated to an arginine-rich cell penetrating peptide;
or a pharmaceutically acceptable salt thereof.
2. The antisense oligonucleotide of claim 1 , wherein the arginine-rich cell penetrating peptide consists of a sequence selected from SEQ ID NOS: 19-34.
3. The antisense oligonucleotide of claim 1 , wherein the arginine-rich cell penetrating peptide utilizes glycine as the linker between the arginine-rich cell penetrating peptide and the antisense oligonucleotide.
4. A pharmaceutical composition comprising the antisense oligonucleotide of claim 1 and a pharmaceutically acceptable carrier.
5. A pharmaceutical composition comprising the antisense oligonucleotide of claim 2 and a pharmaceutically acceptable carrier.
6. A pharmaceutical composition comprising the antisense oligonucleotide of claim 3 and a pharmaceutically acceptable carrier.