SIRT1-saRNA Compositions and Methods of Use

Abstract

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 the sequence of any one of SEQ ID No. 3-24. 
     
     
         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 the sequence of any one of SEQ ID NO: 47-51 or 53-68. 
     
     
         4 . The saRNA of  claim 2 , wherein the saRNA comprises a 3′ overhang. 
     
     
         5 . The saRNA of  claim 4 , wherein the saRNA comprises the sequence of any one of SEQ ID NO: 91-95 or 97-112. 
     
     
         6 . The saRNA of  claim 1 , wherein the saRNA is a saRNA duplex comprising an antisense strand and a sense strand, wherein each strand is independently 14-30 nucleotides in length. 
     
     
         7 . The saRNA of  claim 6 , wherein the antisense strand of the saRNA comprises the sequence of any one of SEQ ID NO: 47-51 or 53-68. 
     
     
         8 . The saRNA of  claim 7 , wherein the sense strand of the saRNA comprises the sequence of any one of SEQ ID NO: 25-29 or 31-46. 
     
     
         9 . The saRNA of  claim 6 , wherein the antisense strand of the saRNA comprises a 3′ overhang. 
     
     
         10 . The saRNA of  claim 9 , wherein the antisense strand of the saRNA comprises the sequence of any one of SEQ ID NO: 91-95 or 97-112. 
     
     
         11 . The saRNA of  claim 10 , wherein the sense strand of the saRNA comprises the sequence of any one of SEQ ID NO: 69-73 or 75-90. 
     
     
         12 . The saRNA of  claim 1 , wherein the saRNA comprises at least one chemical modification. 
     
     
         13 . A pharmaceutical composition comprising the saRNA of  claim 1  and at least one pharmaceutically acceptable excipient. 
     
     
         14 . A method of up-regulating the expression of the SIRT1 gene, comprising administering the saRNA of  claim 1 . 
     
     
         15 . The method of  claim 14 , wherein the expression of the SIRT1 gene is increased by at least 30%. 
     
     
         16 . The method of  claim 14 , wherein the expression of the SIRT1 gene is increased by at least 40%. 
     
     
         17 . The method of  claim 14 , wherein the expression of the SIRT1 gene is increased by at least 50%.