Modulation of eif4e expression

Abstract

Oligomeric compounds, compositions and methods are provided for modulating the expression of eIF4E. The antisense compounds may be single- or double-stranded and are targeted to nucleic acid encoding eIF4E. Methods of using these compounds for modulation of eIF4E expression and for diagnosis and treatment of diseases and conditions associated with expression of eIF4E are provided.

What is claimed is: 
     
         1 . An antisense oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence at least 95% complementary within the 3′ untranslated region (3′UTR) of a nucleic acid encoding human eIF4E, wherein the antisense oligonucleotide comprises at least one chemically modified sugar moiety, internucleoside linkage, or nucleobase. 
     
     
         2 . The antisense oligonucleotide of  claim 1 , wherein the chemically modified sugar moiety is a 2′-O-(2-methoxyethyl) sugar moiety. 
     
     
         3 . The antisense oligonucleotide of  claim 1 , wherein the chemically modified sugar moiety is a bicyclic sugar moiety. 
     
     
         4 . The antisense oligonucleotide of  claim 3 , wherein the bicyclic sugar moiety comprises a 4′-(CH2)-O-2′ or 4′-(CH2)2-O-2′ group. 
     
     
         5 . The antisense oligonucleotide of  claim 1 , wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage. 
     
     
         6 . The antisense oligonucleotide of  claim 1 , wherein the modified nucleobase is a 5-methylcytosine. 
     
     
         7 . The antisense oligonucleotide of  claim 1 , wherein the antisense oligonucleotide is chimeric. 
     
     
         8 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 1 , and a pharmaceutically or physiologically acceptable carrier, diluent, or excipient. 
     
     
         9 . The pharmaceutical composition of  claim 8 , which is in a form suitable for parenteral administration. 
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein said parenteral administration is via intravenous injection or infusion. 
     
     
         11 . The antisense oligonucleotide of  claim 1 , wherein the antisense oligonucleotide has a nucleobase sequence at least 95% complementary within the 3′ untranslated region (3′UTR) of SEQ ID NO: 4 encoding human eIF4E. 
     
     
         12 . The antisense oligonucleotide of  claim 11 , wherein the antisense oligonucleotide has a nucleobase sequence 100% complementary within the 3′ untranslated region (3′UTR) of SEQ ID NO: 4 encoding human eIF4E. 
     
     
         13 . The antisense oligonucleotide of  claim 1 , wherein the antisense oligonucleotide is in the form of a pharmaceutically acceptable salt. 
     
     
         14 . A method for treating a condition or disease associated with eIF4E expression or overexpression with the antisense oligonucleotide of  claim 1 , comprising administering the antisense oligonucleotide to a subject in need thereof. 
     
     
         15 . The method of  claim 14 , wherein said condition or disease associated with eIF4E expression or overexpression is a hyperproliferative condition or disease. 
     
     
         16 . The method of  claim 15 , wherein said hyperproliferative condition or disease is selected from the group consisting of breast cancer, head and neck cancer, colorectal cancer, prostate cancer, lung cancer, bladder cancer, ovarian cancer, renal cancer, and glioblastoma. 
     
     
         17 . A method for treating a condition or disease associated with eIF4E expression or overexpression with the antisense oligonucleotide of  claim 11 , comprising administering the antisense oligonucleotide to a subject in need thereof. 
     
     
         18 . The method of  claim 17 , wherein said hyperproliferative condition or disease is selected from the group consisting of breast cancer, head and neck cancer, colorectal cancer, prostate cancer, lung cancer, bladder cancer, ovarian cancer, renal cancer, and glioblastoma. 
     
     
         19 . A method for treating a condition or disease associated with eIF4E expression or overexpression with the antisense oligonucleotide of  claim 12 , comprising administering the antisense oligonucleotide to a subject in need thereof. 
     
     
         20 . The method of  claim 19 , wherein said hyperproliferative condition or disease is selected from the group consisting of breast cancer, head and neck cancer, colorectal cancer, prostate cancer, lung cancer, bladder cancer, ovarian cancer, renal cancer, and glioblastoma.