Methods and compositions for modulating alpha-1-antitrypsin expression

Abstract

Disclosed herein are methods for decreasing A1AT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of fibrosis. Disclosed herein are methods for decreasing A1AT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of liver disease, such as, A1ATD associated liver disease, and pulmonary disease, such as, A1ATD associated pulmonary disease in an individual in need thereof. Methods for inhibiting A1AT mRNA and protein expression can also be used as a prophylactic treatment to prevent individuals at risk for developing a liver disease, such as, A1ATD associated liver disease and pulmonary disease, such as, A1ATD associated pulmonary disease.

1 - 3 . (canceled) 
     
     
         4 . A compound comprising a modified oligonucleotide consisting of 20 to 30 linked nucleosides and having a nucleobase sequence comprising a portion of at least 20 contiguous nucleobases that is 100% complementary to an equal length portion of nucleobases 1349 to 1597 of SEQ ID NO: 1, and wherein the nucleobase sequence of the modified oligonucleotide is at least 90% complementary to SEQ ID NO: 1, and wherein each nucleotide of the modified oligonucleotide is a modified nucleotide having, independently, a modified sugar moiety, a modified internucleoside linkage, and/or modified nucleobase. 
     
     
         5 - 23 . (canceled) 
     
     
         24 . A composition comprising a compound according to  claim 4  and a pharmaceutically acceptable carrier or diluent. 
     
     
         25 . (canceled) 
     
     
         26 . A method of treating, ameliorating or preventing an A1AT deficiency disease in an animal comprising administering to an animal having or at risk of developing an A1AT deficiency disease a composition according to  claim 24 , and thereby treating, ameliorating, or preventing the A1AT deficiency disease in the animal. 
     
     
         27 - 49 . (canceled)