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 214.
1. A method of treating Duchenne muscular dystrophy, comprising administering an effective amount of an antisense oligonucleotide comprising a base sequence 25 bases in length that is 100% complementary to 25 consecutive bases of a target region of exon 53 of the human dystrophin pre-mRNA, said morpholino antisense oligonucleotide is chemically linked to a polyethylene glycol chain;
wherein the antisense oligonucleotide base sequence comprises at least 20 consecutive bases of C AUU CAA CUG UUG CCU CCG GUU CUG AAG GUG (SEQ ID NO: 193), in which the uracil bases are thymine bases, wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and
wherein the antisense oligonucleotide specifically hybridizes to the target region and induces exon 53 skipping.
2. The method of claim 1 , wherein the antisense oligonucleotide is formulated with a pharmaceutically acceptable carrier or diluent for intravenous administration.
3. The method of claim 2 , wherein the pharmaceutically acceptable carrier or diluent comprises an isotonic saline solution.
4. The method of claim 3 , wherein the isotonic saline solution is phosphate-buffered saline.
5. An injectable solution, comprising:
a) an antisense oligonucleotide comprising a base sequence 25 bases in length that is 100% complementary to 25 consecutive bases of a target region of exon 53 of the human dystrophin pre-mRNA, said morpholino antisense oligonucleotide is chemically linked to a polyethylene glycol chain;
wherein the antisense oligonucleotide base sequence comprises at least 20 consecutive bases of C AUU CAA CUG UUG CCU CCG GUU CUG AAG GUG (SEQ ID NO: 193), in which the uracil bases are thymine bases, wherein the antisense oligonucleotide is a morpholino antisense oligonucleotide, and
wherein the antisense oligonucleotide specifically hybridizes to the target region and induces exon 53 skipping; and
b) a pharmaceutically acceptable carrier or diluent,
wherein the injectable solution is formulated for parenteral administration.
6. The injectable solution of claim 5 , wherein the pharmaceutically acceptable carrier or diluent comprises an isotonic saline solution.
7. The injectable solution of claim 6 , wherein the isotonic saline solution is phosphate-buffered saline.