Modulation of HIF1alpha and HIF2alpha expression

Abstract

Compounds, compositions and methods are provided for modulating the expression of HIF1alpha and/or HIF2alpha. The compositions comprise oligonucleotides, targeted to nucleic acid encoding HIF1alpha and HIF2alpha. Methods of using these compounds for modulation of HIF1alpha and/or HIF2alpha expression and for diagnosis and treatment of disease associated with expression of HIF1alpha and/or HIF2alpha are provided.

1 - 115 . (canceled)  
     
     
         116 . An antisense oligonucleotide 12 to 50 nucleobases in length targeted to at least a portion of nucleotides 2821 to 2859 of a nucleic acid molecule encoding HIF1α (SEQ ID NO: 133).  
     
     
         117 . The antisense oligonucleotide of  claim 116  which is 15 to 30 nucleobases in length.  
     
     
         118 . The antisense oligonucleotide of  claim 116  comprising at least one modified internucleoside linkage, sugar moiety or nucleobase.  
     
     
         119 . The antisense oligonucleotide of  claim 118  wherein said modified internucleoside linkage is a phosphorothioate.  
     
     
         120 . The antisense oligonucleotide of  claim 118  wherein said modified sugar moiety is a 2′-O-methoxyethyl.  
     
     
         121 . The antisense oligonucleotide of  claim 118  wherein said modified nucleobase is a 5-methylcytosine.  
     
     
         122 . The antisense oligonucleotide of  claim 116  which is a chimeric oligonucleotide.  
     
     
         123 . A method of inhibiting expression of HIF1α in a cell or tissue comprising contacting said cell or tissue with the antisense oligonucleotide of  claim 116 .  
     
     
         124 . A method of inhibiting or preventing aberrant angiogenesis in an animal, comprising administering to said animal a composition comprising the antisense oligonucleotide of  claim 116 .  
     
     
         125 . A method of preventing, ameliorating or treating an ocular disorder, comprising administration to a subject in need of such treatment a composition comprising the antisense oligonucleotide of  claim 116 .  
     
     
         126 . The method of  claim 125  wherein the ocular disorder is selected from the group consisting of macular degeneration, diabetic retinopathy and retinopathy of prematurity.  
     
     
         127 . A kit or assay device comprising the antisense oligonucleotide of  claim 116 .  
     
     
         128 . a composition comprising the antisense oligonucleotide of  claim 116  and a pharmaceutically acceptable carrier.  
     
     
         129 . An antisense oligonucleotide 16, 17, 18, 19, 20, 21, 22, 23, 24 or 25 nucleobases in length targeted to a nucleic acid molecule encoding HIF1α (SEQ ID NO: 133), wherein said antisense oligonucleotide has at least 80% identity with SEQ ID NO: 189.  
     
     
         130 . The antisense oligonucleotide of  claim 129  which is 18, 19, 20, 21 or 22 nucleotides in length and has at least 90% identity with SEQ ID NO: 189.  
     
     
         131 . The antisense oligonucleotide of  claim 130  which is 19, 20 or 21 nucleotides in length and has at least 95% identity with SEQ ID NO: 189.  
     
     
         132 . An antisense oligonucleotide with a nucleotide sequence consisting of SEQ ID NO: 189.  
     
     
         133 . The antisense oligonucleotide of  claim 132  comprising a central region of ten 2′-deoxynucleotides which is flanked on each side by five 2′-O-methoxyethyl nucleotides, wherein the internucleoside linkages of said oligonucleotide are phosphorothioate throughout the oligonucleotide and the cytidine residues of 5-methylcytidines.  
     
     
         134 . A pharmaceutical composition comprising the antisense oligonucleotide of  claim 133.