Modulation of transthyretin expression

Abstract

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

1 - 18 . (canceled) 
     
     
         19 . An antisense compound comprising a modified oligonucleotide 20 to 25 nucleobases in length, wherein the modified oligonucleotide has at least a 13-nucleobase portion of SEQ ID NO: 75 and is at least 95% complementary to SEQ ID NO: 4, and wherein the modified oligonucleotide comprises at least one modified sugar moiety. 
     
     
         20 . The antisense compound of  claim 19 , wherein each “T” of SEQ ID NO: 75 is a uracil. 
     
     
         21 . The antisense compound of  claim 19 , wherein at least one modified sugar moiety comprises a 2′-O—CH 3  modification. 
     
     
         22 . The antisense compound of  claim 20 , wherein at least one modified sugar moiety comprises a 2′-O—CH 3  modification. 
     
     
         23 . The antisense compound of  claim 19 , wherein:
 the modified oligonucleotide is 21 nucleobases in length;   the modified oligonucleotide has at least a 13-nucleobase portion of SEQ ID NO: 75 and is at least 95% complementary to SEQ ID NO: 4, wherein each “T” of SEQ ID NO: 75 is a uracil; and   the modified oligonucleotide comprises at least one 2′-O—CH 3  modified sugar moiety.   
     
     
         24 . The antisense compound of  claim 19 , wherein the antisense compound is single-stranded. 
     
     
         25 . The antisense compound of  claim 20 , wherein the antisense compound is single-stranded. 
     
     
         26 . The antisense compound of  claim 21 , wherein the antisense compound is single-stranded. 
     
     
         27 . The antisense compound of  claim 22 , wherein the antisense compound is single-stranded. 
     
     
         28 . The antisense compound of  claim 23 , wherein the antisense compound is single-stranded. 
     
     
         29 . A compound comprising a nanoparticle and the antisense compound of  claim 19 . 
     
     
         30 . A compound comprising a nanoparticle and the antisense compound of  claim 23 . 
     
     
         31 . A compound comprising a nanoparticle and the antisense compound of  claim 28 . 
     
     
         32 . A compound comprising a liposome and the antisense compound of  claim 19 . 
     
     
         33 . A compound comprising a liposome and the antisense compound of  claim 23 . 
     
     
         34 . A compound comprising a liposome and the antisense compound of  claim 28 . 
     
     
         35 . A method of inhibiting the expression of human transthyretin in a cell or tissue comprising contacting said cell or tissue with the antisense compound of  claim 19 , thereby inhibiting expression of human transthyretin in the cell or tissue. 
     
     
         36 . A method of inhibiting the expression of human transthyretin in a cell or tissue comprising contacting said cell or tissue with the antisense compound of  claim 23 , thereby inhibiting expression of human transthyretin in the cell or tissue. 
     
     
         37 . A method of inhibiting the expression of human transthyretin in a cell or tissue comprising contacting said cell or tissue with the antisense compound of  claim 28 , thereby inhibiting expression of human transthyretin in the cell or tissue. 
     
     
         38 . A method of inhibiting the expression of human transthyretin in a cell or tissue comprising contacting said cell or tissue with the compound of  claim 29 , thereby inhibiting expression of human transthyretin in the cell or tissue. 
     
     
         39 . A method of inhibiting the expression of human transthyretin in a cell or tissue comprising contacting said cell or tissue with the compound of  claim 30 , thereby inhibiting expression of human transthyretin in the cell or tissue. 
     
     
         40 . A method of inhibiting the expression of human transthyretin in a cell or tissue comprising contacting said cell or tissue with the compound of  claim 31 , thereby inhibiting expression of human transthyretin in the cell or tissue. 
     
     
         41 . A method of inhibiting the expression of human transthyretin in a cell or tissue comprising contacting said cell or tissue with the compound of  claim 32 , thereby inhibiting expression of human transthyretin in the cell or tissue. 
     
     
         42 . A method of inhibiting the expression of human transthyretin in a cell or tissue comprising contacting said cell or tissue with the compound of  claim 33 , thereby inhibiting expression of human transthyretin in the cell or tissue. 
     
     
         43 . A method of inhibiting the expression of human transthyretin in a cell or tissue comprising contacting said cell or tissue with the compound of  claim 34 , thereby inhibiting expression of human transthyretin in the cell or tissue.