Antisense modulation of calreticulin expression

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of calreticulin. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding calreticulin. Methods of using these compounds for modulation of calreticulin expression and for treatment of diseases associated with expression of calreticulin are provided.

1 . An antisense compound 8 to 30 nucleobases in length targeted to the 5′-untranslated region, coding region, stop codon or 3′ untranslated region of a nucleic acid molecule encoding human calreticulin, wherein said antisense compound specifically hybridizes with and inhibits the expression of human calreticulin.  
     
     
         2 . The antisense compound of  claim 1  which is an antisense oligonucleotide.  
     
     
         3 . The antisense compound of  claim 2  wherein the antisense oligonucleotide has a sequence comprising SEQ ID NO: 11, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33,. 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 79, 80, 81, 82, 83, 84, 85, 86, 87 or 88.  
     
     
         4 . The antisense compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.  
     
     
         5 . The antisense compound of  claim 4  wherein the modified internucleoside linkage is a phosphorothioate linkage.  
     
     
         6 . The antisense compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified sugar moiety.  
     
     
         7 . The antisense compound of  claim 6  wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.  
     
     
         8 . The antisense compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified nucleobase.  
     
     
         9 . The antisense compound of  claim 8  wherein the modified nucleobase is a 5-methylcytosine.  
     
     
         10 . The antisense compound of  claim 2  wherein the antisense oligonucleotide is a chimeric oligonucleotide.  
     
     
         11 . A pharmaceutical composition comprising the antisense compound of  claim 1  and a pharmaceutically acceptable carrier or diluent.  
     
     
         12 . The pharmaceutical composition of  claim 11  further comprising a colloidal dispersion system.  
     
     
         13 . The pharmaceutical composition of  claim 11  wherein the antisense compound is an antisense oligonucleotide.  
     
     
         14 . A method of inhibiting the expression of calreticulin in human cells or tissues comprising contacting said cells or tissues with the antisense compound of  claim 1  so that expression of calreticulin is inhibited.  
     
     
         15 . A method of treating a human having a disease or condition associated with calreticulin comprising administering to said animal a therapeutically or prophylactically effective amount of the antisense compound of  claim 1  so that expression of calreticulin is inhibited.  
     
     
         16 . The method of  claim 15  wherein the disease or condition is a hyperproliferative disorder.  
     
     
         17 . The method of  claim 16  wherein the hyperproliferative disorder is cancer.  
     
     
         18 . The method of  claim 15  wherein the disease or condition is an autoimmune disease.  
     
     
         19 . The method of  claim 15  wherein the disease or condition is a viral infection.  
     
     
         20 . The method of  claim 15  wherein the disease or condition is a cardiovascular disease.