Modulation of insulin like growth factor i receptor expression

Abstract

The present invention provides compositions and methods for modulating the expression of growth factor gene. In particular, this invention relates to compounds, particularly oligonucleotide compounds, which, in preferred embodiments, hybridize with nucleic acid molecules encoding the Insulin Like Growth Factor I receptor (IGF-I receptor or IGF-IR) and in particular human IGF-IR. Such compounds are exemplified herein to modulate proliferation which is relevant to the treatment of proliferative and inflammatory skin disorders and cancer. It will be understood, however, that the compounds can be used for any other condition in which the IGF-IR is involved including inflammatory condition.

1 - 44 . (canceled) 
     
     
         45 . An antisense oligonucleotide comprising 20 to 80 nucleobases in length targeted to a nucleic acid molecule encoding human insulin-like growth factor receptor (IGF-IR), wherein said oligonucleotide specifically hybridizes with said nucleic acid molecule and inhibits the expression of IGF-IR and wherein said oligonucleotide comprises a deoxynucleotide region flanked on both the 5′ and the 3′ ends of said deoxynucleotide region with 2′-O-(2-methoxyethyl) nucleotides. 
     
     
         46 . The oligonucleotide as claimed in  claim 45 , wherein the oligonucleotide is 20 to 30 nucleobases in length. 
     
     
         47 . The oligonucleotide as claimed in  claim 45 , wherein the oligonucleotide is 8 to 30 nucleobases in length. 
     
     
         48 . The oligonucleotide as claimed in  claim 45 , wherein said oligonucleotide comprises a ten deoxynucleotide region flanked on both the 5′ and the 3′ ends of said ten deoxynucleotide region with five 2′-O-(2-methoxyethyl) nucleotides. 
     
     
         49 . The oligonucleotide of  claim 45  which is a DNA oligonucleotide, an RNA oligonucleotide or a chimeric oligonucleotide. 
     
     
         50 . The oligonucleotide of  claim 45 , wherein the nucleic acid molecule is an RNA molecule encoding human insulin-like growth factor receptor. 
     
     
         51 . The oligonucleotide of  claim 50 , wherein at least a portion of said oligonucleotide hybridizes with the nucleic acid molecule to form an oligonucleotide-RNA duplex. 
     
     
         52 . The oligonucleotide of  claim 45 , wherein each internucleoside linkage in said oligonucleotide is a phosphorothioate and each cytosine in said oligonucleotide is a 5-methylcytosine. 
     
     
         53 . The oligonucleotide of  claim 45 , wherein said oligonucleotide is targeted to a coding region of said nucleic acid molecule. 
     
     
         54 . The oligonucleotide of  claim 53 , wherein said oligonucleotide is selected from SEQ ID NO:26, SEQ ID NO:43, SEQ ID NO:50, SEQ ID NO:53, SEQ ID NO:68 and SEQ ID NO:72. 
     
     
         55 . The oligonucleotide of  claim 45 , wherein said oligonucleotide is targeted to the 5′ UTR of said nucleic acid molecule. 
     
     
         56 . The oligonucleotide of  claim 55 , wherein said oligonucleotide is selected from SEQ ID NO:110, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:122 and SEQ ID NO:131. 
     
     
         57 . A composition comprising the oligonucleotide of  claim 45  or a salt thereof and a pharmaceutically acceptable carrier or diluent. 
     
     
         58 . A diagnostic in vitro method for identifying a disease state comprising identifying the presence of IGF-IR in a sample using an oligonucleotide of  claim 45 . 
     
     
         59 . A kit or assay device comprising the oligonucleotide of  claim 45 . 
     
     
         60 . A method of treating an animal having a disease, condition or disorder associated with IGF-IR, the method comprising administering to the animal an oligonucleotide of  claim 45 , wherein said oligonucleotide inhibits expression of IGF-IR and wherein the disorder associated with IGF-IR is a skin disorder selected from psoriasis, ichthyosis, pityriasis, rubra, pilaris, serborrhoea, keloids, keratosis, neoplasias, scleroderma, warts, benign growths or cancers of the skin. 
     
     
         61 . The method of  claim 60 , wherein the animal or mammal is a human. 
     
     
         62 . The method of  claim 60 , wherein the oligonucleotide is a phosphorothioate nucleic acid molecule.