Human rnase iii and compositions and uses thereof

Abstract

The present invention provides polynucleotides encoding human RNase III and polypeptides encoded thereby. Methods of using said polynucleotides and polypeptides are also provided.

1 - 64 . (canceled) 
     
     
         65 . A method comprising contacting a cell with a modified oligonucleotide wherein:
 the modified oligonucleotide is 12 to 30 nucleobases in length;   the modified oligonucleotide is complementary to nucleobases 3051 to 4004 of SEQ ID NO: 1 or to nucleobases 4197 to 4397 of SEQ ID NO: 1.   
     
     
         66 . The method of  claim 65  wherein the modified oligonucleotide is complementary to nucleobases 3051 to 4004 of SEQ ID NO: 1. 
     
     
         67 . The method of  claim 66  wherein in the modified oligonucleotide comprises the nucleobase sequence of SEQ ID NO: 8 or 9. 
     
     
         68 . The method of  claim 65  wherein the modified oligonucleotide is complementary to nucleobases 4197 to 4397 of SEQ ID NO: 1. 
     
     
         69 . The method of  claim 68  wherein the modified oligonucleotide comprises the nucleobase sequence of SEQ ID NO: 12, 13, 14, or 15. 
     
     
         70 . The method of  claim 65 , wherein the modified oligonucleotide comprises at least one nucleoside comprising a modified sugar. 
     
     
         71 . The method of  claim 70 , wherein at least one modified nucleoside comprises a 2′-O-methoxyethyl. 
     
     
         72 . The method of  claim 65  wherein the modified oligonucleotide comprises at least one modified internucleoside linkage. 
     
     
         73 . The method of  claim 65 , wherein the modified oligonucleotide comprises:
 a gap segment consisting of linked deoxynucleosides;   a 5′ wing segment consisting of linked modified nucleosides; and   a 3′ wing segment consisting of linked modified nucleosides;   
       wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each modified nucleoside of each wing segment comprises a modified sugar. 
     
     
         74 . The method of  claim 73 , wherein each modified sugar comprises a 2′-modification. 
     
     
         75 . The method of  claim 74 , wherein each 2′-modification is a 2′-O-methoxyethyl modification. 
     
     
         76 . The method of  claim 65 , wherein the cell is in an animal. 
     
     
         77 . The method of  claim 76 , wherein the animal is a mammal. 
     
     
         78 . The method of  claim 77 , wherein the animal is a human.