Antisense oligonucleotides for inducing exon skipping and methods of use thereof
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. An antisense oligonucleotide of 24 bases comprising the base sequence GAU AGG UGG UAU CAA CAU CUG UAA (SEQ ID NO: 1), in which the uracil bases are thymine bases, and wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide.
2. The antisense oligonucleotide of claim 1 , 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.
3. The antisense oligonucleotide of claim 1 , wherein the oligonucleotide is chemically linked to a polyethylene glycol chain.
4. An antisense oligonucleotide of 21 bases comprising the base sequence GAU AGG UGG UAU CAA CAU CUG (SEQ ID NO: 2), in which the uracil bases are thymine bases, and wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide.
5. The antisense oligonucleotide of claim 4 , 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.
6. The antisense oligonucleotide of claim 4 , wherein the oligonucleotide is chemically linked to a polyethylene glycol chain.
7. An antisense oligonucleotide of 25 bases comprising the base sequence GAU AGG UGG UAU CAA CAU CUG UAA G (SEQ ID NO: 3), in which the uracil bases are thymine bases, and wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide.
8. The antisense oligonucleotide of claim 7 , 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.
9. The antisense oligonucleotide of claim 7 , wherein the oligonucleotide is chemically linked to a polyethylene glycol chain.
10. An antisense oligonucleotide of 20 bases comprising the base sequence GGU GGU AUC AAC AUC UGU AA (SEQ ID NO: 4), in which the uracil bases are thymine bases, and wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide.
11. The antisense oligonucleotide of claim 10 , 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.
12. The antisense oligonucleotide of claim 10 , wherein the oligonucleotide is chemically linked to a polyethylene glycol chain.
13. A pharmaceutical composition comprising an antisense oligonucleotide of 20 to 50 bases comprising at least 17 consecutive bases of the base sequence GAU AGG UGG UAU CAA CAU CUG UAA (SEQ ID NO: 1), in which the uracil bases are optionally thymine bases, wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and wherein the antisense oligonucleotide specifically hybridizes to a target region in exon 8 of the human dystrophin gene inducing exon 8 skipping, and a pharmaceutically acceptable carrier.
14. The pharmaceutical composition of claim 13 , 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.
15. The pharmaceutical composition of claim 13 , wherein the oligonucleotide is chemically linked to a polyethylene glycol chain.
16. A pharmaceutical composition comprising an antisense oligonucleotide of 21 bases comprising the base sequence AGG UGG UAU CAA CAU CUG (SEQ ID NO: 2 ), in which the uracil bases are thymine bases, and wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and a pharmaceutically acceptable carrier.
17. The pharmaceutical composition of claim 16 , 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.
18. The pharmaceutical composition of claim 16 , wherein the oligonucleotide is chemically linked to a polyethylene glycol chain.
19. A pharmaceutical composition comprising an antisense oligonucleotide of 25 bases comprising the base sequence GAU AGG UGG UAU CAA CAU CUG UAA G (SEQ ID NO: 3), in which the uracil bases are thymine bases, and wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and a pharmaceutically acceptable carrier.
20. The pharmaceutical composition of claim 19 , 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.
21. The pharmaceutical composition of claim 19 , wherein the oligonucleotide is chemically linked to a polyethylene glycol chain.
22. A pharmaceutical composition comprising an antisense oligonucleotide of 20 bases comprising the base sequence GGU GGU AUC AAC AUC UGU AA (SEQ ID NO: 4), in which the uracil bases are thymine bases, and wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and a pharmaceutically acceptable carrier.
23. The pharmaceutical composition of claim 22 , 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.
24. The pharmaceutical composition of claim 22 , wherein the oligonucleotide is chemically linked to a polyethylene glycol chain.