SIRT1-saRNA compositions and methods of use
The invention relates to a saRNAs useful in upregulating the expression of the SIRT1 gene and therapeutic compositions comprising the saRNA. Methods of using the saRNA and the therapeutic compositions are also provided.
1. A synthetic isolated saRNA which up-regulates the expression of the SIRT1 gene, wherein the saRNA comprises a strand that is at least 80% complementary to a targeted sequence on the template strand of the SIRT1 gene, wherein the targeted sequence comprises SEQ ID No. 8, and wherein the saRNA comprises SEQ ID NO: 52.
2. The saRNA of claim 1 , wherein the saRNA is single-stranded and comprises 14-30 nucleotides in length.
3. The saRNA of claim 2 , wherein the saRNA comprises a 3′ overhang.
4. The saRNA of claim 3 , wherein the saRNA comprises SEQ ID NO: 96.
5. The saRNA of claim 1 , wherein the saRNA is a saRNA duplex comprising an antisense strand and a sense strand, wherein the antisense strand comprises SEQ ID NO: 52, and wherein each strand is independently 14-30 nucleotides in length.
6. The saRNA of claim 5 , wherein the sense strand of the saRNA comprises SEQ ID NO: 30.
7. The saRNA of claim 5 , wherein the antisense strand of the saRNA comprises a 3′ overhang.
8. The saRNA of claim 7 , wherein the antisense strand of the saRNA comprises SEQ ID NO: 96.
9. The saRNA of claim 8 , wherein the sense strand of the saRNA comprises SEQ ID NO: 74.
10. The saRNA of claim 1 , wherein the saRNA comprises at least one chemical modification.
11. A pharmaceutical composition comprising the saRNA of claim 1 and at least one pharmaceutically acceptable excipient.
12. A method of up-regulating the expression of the SIRT1 gene, comprising administering the saRNA of claim 1 .
13. The method of claim 12 , wherein the expression of the SIRT1 gene is increased by at least 30%.
14. The method of claim 12 , wherein the expression of the SIRT1 gene is increased by at least 40%.
15. The method of claim 12 , wherein the expression of the SIRT1 gene is increased by at least 50%.