Modulation of sglt-2 expression

Abstract

Compounds, compositions and methods are provided for modulating the expression of SGLT2. The compositions comprise oligonucleotides, targeted to nucleic acid encoding SGLT2. Methods of using these compounds for modulation of SGLT2 expression and for diagnosis and treatment of diseases and conditions associated with expression of SGLT2 are provided.

1 . A modified oligonucleotide 8 to 80 nucleobases in length targeted to a nucleic acid molecule encoding SGLT2, wherein the modified oligonucleotide is complementary to at least an 8 nucleobase portion of SEQ ID NO: 4 encoding SGLT2 and comprises at least one modified internucleoside linkage, sugar moiety, or nucleobase. 
     
     
         2 . The modified oligonucleotide of  claim 1  comprising 10 to 50 nucleobases in length. 
     
     
         3 . The modified oligonucleotide of  claim 2  comprising 13 to 30 nucleobases in length. 
     
     
         4 . The modified oligonucleotide of  claim 3  comprising 15 to 25 nucleobases in length. 
     
     
         5 . The modified oligonucleotide of  claim 4  comprising 18 to 22 nucleobases in length. 
     
     
         6 . (canceled) 
     
     
         7 . The modified oligonucleotide of  claim 1  comprising a DNA oligonucleotide. 
     
     
         8 . The modified oligonucleotide of  claim 1  comprising an RNA oligonucleotide. 
     
     
         9 . The modified oligonucleotide of  claim 1  comprising a chimeric oligonucleotide. 
     
     
         10 - 15 . (canceled) 
     
     
         16 . The modified oligonucleotide of  claim 1  comprising at least one 2′-O-methoxyethyl sugar moiety. 
     
     
         17 . The modified oligonucleotide of  claim 1  comprising at least one phosphorothioate internucleoside linkage. 
     
     
         18 . The modified oligonucleotide of  claim 1  wherein at least one cytosine is a 5-methylcytosine. 
     
     
         19 - 38 . (canceled) 
     
     
         39 . A method of preventing or delaying the onset of a disease or condition in an animal comprising administering to the animal an effective amount of an oligonucleotide 8 to 80 nucleobases in length targeted to a nucleic acid molecule encoding SGLT2, wherein the oligonucleotide is complementary to at least an 8 nucleobase portion of SEQ ID NO: 4 encoding SGLT2 so that expression of SGLT2 is inhibited, wherein the disease or condition is associated with expression of SGLT2 in the kidney. 
     
     
         40 . (canceled) 
     
     
         41 . A method of preventing or delaying the onset of type 2 diabetes in an animal comprising administering to the animal an oligonucleotide 8 to 80 nucleobases in length targeted to a nucleic acid molecule encoding SGLT2, wherein the oligonucleotide is complementary to at least an 8 nucleobase portion of SEQ ID NO: 4 encoding SGLT2 so that expression of SGLT2 is inhibited. 
     
     
         42 . The method of  claim 41  wherein said animal is a primate or a rodent. 
     
     
         43 . (canceled) 
     
     
         44 . A method of preventing or delaying the onset of an increase in blood glucose level in an animal comprising administering to the animal an oligonucleotide 8 to 80 nucleobases in length targeted to a nucleic acid molecule encoding SGLT2, wherein the oligonucleotide is complementary to at least an 8 nucleobase portion of SEQ ID NO: 4 encoding SGLT2 so that expression of SGLT2 is inhibited. 
     
     
         45 . The method of  claim 44  wherein the animal is a primate or a rodent. 
     
     
         46 . The method of  claim 44  wherein the blood glucose level is plasma glucose level or serum glucose level. 
     
     
         47 . The method of  claim 44  wherein the animal is a diabetic animal. 
     
     
         48 . The method of  claim 44  wherein the animal is insulin-resistant as compared to a normal animal. 
     
     
         49 . (canceled) 
     
     
         50 . A method of decreasing blood glucose level in an animal comprising administering to the animal an oligonucleotide 8 to 80 nucleobases in length targeted to a nucleic acid molecule encoding SGLT2, wherein the oligonucleotide is complementary to at least an 8 nucleobase portion of SEQ ID NO: 4 encoding SGLT2 so that expression of SGLT2 is inhibited. 
     
     
         51 . The method of  claim 50  wherein the animal is a primate or a rodent. 
     
     
         52 . The method of  claim 50  wherein the blood glucose level is plasma glucose level or serum glucose level. 
     
     
         53 . The method of  claim 50  wherein the animal is a diabetic animal. 
     
     
         54 . The method of  claim 50  wherein the animal is insulin-resistant as compared to a normal animal. 
     
     
         55 . (canceled) 
     
     
         56 . (canceled)