Modulation of apolipoprotein(a) expression

Abstract

Compounds, compositions and methods are provided for modulating the expression of apolipoprotein(a). The compositions comprise oligonucleotides, targeted to nucleic acid encoding apolipoprotein(a). Methods of using these compounds for modulation of apolipoprotein(a) expression and for diagnosis and treatment of disease associated with expression of apolipoprotein(a) are provided.

1 . A compound 8 to 80 nucleobases in length targeted to a nucleic acid molecule encoding apolipoprotein(a), wherein said compound is at least 70% complementary to said nucleic acid molecule encoding apolipoprotein(a), and wherein said compound comprises at least an 8 nb sequence selected from any of SEQ ID NOs: 13-22, 24-38, 41-45. 
     
     
         2 . The compound of  claim 1  comprising 12 to 50 nucleobases in length. 
     
     
         3 . The compound of  claim 2  comprising 15 to 30 nucleobases in length. 
     
     
         4 . The compound of  claim 1  comprising an oligonucleotide. 
     
     
         5 . The compound of  claim 4  comprising an antisense oligonucleotide. 
     
     
         6 .- 7 . (canceled) 
     
     
         8 . The compound of  claim 4  comprising a chimeric oligonucleotide. 
     
     
         9 . (canceled) 
     
     
         10 . The compound of  claim 1  having at least 80%, at least 90%, at least 95%, at least 99% or 100% complementarity with said nucleic acid molecule encoding apolipoprotein(a). 
     
     
         11 .- 13 . (canceled) 
     
     
         14 . The compound of  claim 1  having at least one modified internucleoside linkage, sugar moiety, or nucleobase. 
     
     
         15 . The compound of  claim 1  having at least one 2′-O-methoxyethyl sugar moiety. 
     
     
         16 . The compound of  claim 1  having at least one phosphorothioate internucleoside linkage. 
     
     
         17 . The compound of  claim 1  having at least one 5-methylcytosine. 
     
     
         18 .- 24 . (canceled) 
     
     
         25 . A method of inhibiting the expression of apolipoprotein(a) in a cell or tissue comprising contacting said cell or tissue with the compound of  claim 1  so that expression of apolipoprotein(a) is inhibited. 
     
     
         26 .- 28 . (canceled) 
     
     
         29 . A kit or assay device comprising the compound of  claim 1 . 
     
     
         30 . A method of treating an animal having a disease or condition associated with apolipoprotein(a) comprising administering to said animal a therapeutically or prophylactically effective amount of the compound of  claim 1  so that expression of apolipoprotein(a) is inhibited. 
     
     
         31 . (canceled) 
     
     
         32 . The method of  claim 30 , wherein the disease or condition is a cardiovascular disorder, atherosclerosis, hypercholesterolimia, coronary artery disease or any combination thereof. 
     
     
         33 . A method of inhibiting the expression of apolipoprotein(a) comprising contacting a biological system expressing human apolipoprotein(a) with a synthetic antisense compound, wherein said synthetic antisense compound comprises from 15 to 30 nucleobases in length and has at least 3 mismatches to human plasminogen and wherein the compound comprises at least an 8 nb sequence selected from any of SEQ ID NOs: 13-22, 24-38, 41-45. 
     
     
         34 . The method of  claim 33  wherein the biological system is a human. 
     
     
         35 . (canceled)