SIRT1-SARNA COMPOSITIONS AND METHODS OF USE
The disclosure 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 comprise 14-30 nucleotides in length and comprises SEQ ID NO: 114 or 116.
2 . The saRNA of claim 1 , wherein the saRNA is double-stranded and further comprises a sense strand.
3 . The saRNA of claim 2 , wherein the sense strand of the saRNA comprises SEQ ID NO: 113 or 115.
4 . A pharmaceutical composition comprising the saRNA of claim 1 and at least one pharmaceutically acceptable excipient.
5 . A method of up-regulating the expression of the SIRT1 gene, comprising administering the saRNA of claim 1 .
6 . The method of claim 5 , wherein the expression of the SIRT1 gene is increased by at least 30%, 40%, or 50%.
7 . A method of treating or preventing non-alcoholic fatty liver disease (NAFLD), comprising administering 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 and the strand comprise 14-30 nucleotides in length.
8 . The method of claim 7 , wherein the strand of the saRNA comprises SEQ ID NO: 96, 114 or 116.
9 . The method of claim 8 , wherein the saRNA is double-stranded and further comprises a sense strand.
10 . The method of claim 7 , wherein the sense strand of the saRNA comprises SEQ ID
11 . A method of treating or preventing inflammation, comprising administering 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 and the strand comprise 14-30 nucleotides in length.
12 . The method of claim 11 , wherein the level of TNFa, IL-1β, IL-6, KC, MCP1, pNFKB or pJNK is reduced.
13 . The method of claim 11 , wherein the strand of the saRNA comprises SEQ ID NO: 96, 114 or 116.
14 . The method of claim 13 , wherein the saRNA is double-stranded and further comprises a sense strand.
15 . The method of claim 14 , wherein the sense strand of the saRNA comprises SEQ ID NO: 74, 113 or 115.