Targeting MicroRNAs for the Treatment of Fibrosis

Abstract

Provided herein are compositions and methods for the modulation of miR-214 for the treatment and/or prevention of fibrosis and fibroproliferative conditions.

1 .- 25 . (canceled) 
     
     
         26 . A method of preventing metastasis of a cancer cell comprising contacting a cancer cell with a compound comprising a modified oligonucleotide consisting of 8 to 25 linked nucleosides, wherein the nucleobase sequence of the modified oligonucleotide is complementary to the nucleobase sequence of miR-214, thereby preventing metastasis of the cancer cell. 
     
     
         27 . The method of  claim 26 , wherein the cancer cell is in vivo. 
     
     
         28 . A method of preventing metastasis comprising administering to a subject having cancer a compound comprising a modified oligonucleotide consisting of 8 to 25 linked nucleosides, wherein the nucleobase sequence of the modified oligonucleotide is complementary to the nucleobase sequence of miR-214, thereby preventing metastasis the cancer. 
     
     
         29 . The method of  claim 28 , wherein the cancer is selected from liver cancer, breast cancer, lung cancer, colon cancer, ovarian cancer, cervical cancer, brain cancer, esophageal cancer, kidney cancer, melanoma, oral cancer, pancreatic cancer, prostate cancer, rectal cancer, stomach cancer, bladder cancer, thyroid cancer, and testicular cancer. 
     
     
         30 . The method of  claim 28 , wherein the compound consists of the modified oligonucleotide. 
     
     
         31 . The method of  claim 28 , wherein the nucleobase sequence of the modified oligonucleotide is at least 90% complementary to a nucleobase sequence selected from SEQ ID NO: 1 and 2. 
     
     
         32 . The method of  claim 28 , wherein the nucleobase sequence of the modified oligonucleotide is fully complementary to a nucleobase sequence selected from SEQ ID NO: 1 and 2. 
     
     
         33 . The method of  claim 28 , wherein the nucleobase sequence of the modified oligonucleotide
 a. has a nucleobase sequence comprising a nucleobase sequence selected from SEQ ID NOs: 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18; or   b. has a nucleobase sequence consisting of a nucleobase sequence selected from SEQ ID NOs: 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, and 17.   
     
     
         34 . The method of  claim 28 , wherein the modified oligonucleotide consists of 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 linked nucleosides. 
     
     
         35 . The method of  claim 28 , wherein the modified oligonucleotide comprises at least one modified internucleoside linkage. 
     
     
         36 . The method of  claim 28 , wherein each internucleoside linkage of the modified oligonucleotide is a modified internucleoside linkage. 
     
     
         37 . The method of  claim 28 , wherein the modified oligonucleotide comprises at least one nucleoside comprising a modified sugar. 
     
     
         38 . The method of  claim 37 , wherein each modified sugar is independently selected from a 2′-O-methoxyethyl sugar, a 2′-fluoro sugar, 2′-O-methyl sugar, and a bicyclic sugar moiety. 
     
     
         39 . The method of  claim 38  wherein the bicyclic sugar moiety is independently selected from an LNA sugar moiety and a cEt sugar moiety. 
     
     
         40 . The method of  claim 39  wherein the cEt sugar moiety is independently selected from an S-cEt sugar moiety and an R-cEt sugar moiety. 
     
     
         41 . The method of  claim 28 , wherein the modified oligonucleotide comprises a seed match sequence. 
     
     
         42 . The method of  claim 41 , wherein the seed match sequence is selected from SEQ ID NOs: 17, 18, 26, 27, 29, 29 and 30. 
     
     
         43 . The method of  claim 28 , wherein the administration comprises parenteral administration. 
     
     
         44 . (canceled)