Splice-switching oligonucleotides and methods of use
The present disclosure provides methods and compositions for the treatment of cancer. In some aspects, the present disclosure provides splice-switching oligonucleotides that downregulate AR or EGFR expression and methods of using these splice-switching oligonucleotides to treat cancer.
1. A modified splice-switching oligonucleotide selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5 wherein the splice-switching oligonucleotide comprising a 2′-O-Me phosphorothioate backbone, and wherein the splice-switching oligonucleotide can reduce expression of the active form of androgen receptor or EGFR in a cancer cell.
2. The modified splice-switching oligonucleotide of claim 1 , wherein the oligonucleotide comprises SEQ ID NO: 3.
3. The modified splice-switching oligonucleotide of claim 1 , wherein the oligonucleotide comprises SEQ ID NO: 4.
4. The modified splice-switching oligonucleotide of claim 1 , wherein the oligonucleotide comprises SEQ ID NO: 5.
5. A composition comprising the splice-switching oligonucleotide of claim 1 .
6. The composition of claim 5 , wherein the composition further comprises a pharmaceutically acceptable carrier.
7. A method of treating a subject suffering from cancer comprising administering to the subject a therapeutically effective amount of a splice-switching oligonucleotide of claim 1 such that the cancer is treated.
8. The method according to claim 7 , wherein the cancer comprises prostate cancer.
9. The method of claim 7 , wherein the subject is an African American male suffering from prostate cancer.
10. The method of claim 7 , wherein the method further comprises administering to the subject a second cancer therapy.
11. A method of treating a subject suffering from a cancer, comprising administering to the subject a therapeutically effective amount of a composition comprising a splice-switching oligonucleotide of claim 1 and a second cancer therapy in an amount effective to treat the cancer.