Methods and compositions for the treatment of cancer or other diseases

Abstract

The present invention relates to methods and compositions for the treatment of diseases, including cancer, infectious diseases and autoimmune diseases. The present invention also relates to methods and compositions for improving immune function. More particularly, the present invention relates to multifunctional molecules that are capable of being delivered to cells of interest for the treatment of diseases and for the improvement in immune function.

1 .- 28 . (canceled) 
     
     
         29 . A molecule comprising:
 (i) a targeting moiety covalently bound to a first oligonucleotide through a linker; and   (ii) a second complementary oligonucleotide hybridized to said first oligonucleotide to form a double-stranded oligonucleotide bound to said targeting moiety.   
     
     
         30 . The molecule of  claim 29 , wherein said targeting moiety is covalently bound to the 5′ end of said first oligonucleotide through said linker. 
     
     
         31 . The molecule of  claim 30 , wherein said targeting moiety is a CpG oligodeoxynucleotide or an aptamer. 
     
     
         32 . The molecule of  claim 31 , wherein said targeting moiety is a phosphorothioated oligodeoxynucleotide. 
     
     
         33 . The molecule of  claim 32 , wherein said oligodeoxynucleotide is about 8 to 40 base pairs in length. 
     
     
         34 . The molecule of  claim 33 , wherein said targeting moiety is a Toll-like receptor ligand. 
     
     
         35 . The molecule of  claim 34 , wherein said targeting moiety is capable of delivering the molecule to a cell of interest. 
     
     
         36 . The molecule of  claim 35 , wherein said cell is a dendritic cell, a macrophage, a monocyte, a B cell, a T cell, an endothelial cell, or a malignant derivative thereof. 
     
     
         37 . The molecule of  claim 29 , wherein said second complementary oligonucleotide comprises 2′-fluoro, 2-O-methyl or locked nucleic acid. 
     
     
         38 . The molecule of  claim 37 , wherein said double-stranded oligonucleotide is a siRNA. 
     
     
         39 . The molecule of  claim 38 , wherein said double-stranded oligonucleotide is about 19 to 30 base pairs in length. 
     
     
         40 . (canceled) 
     
     
         41 . A pharmaceutical composition comprising the molecule of  claim 29  and a pharmaceutically acceptable carrier. 
     
     
         42 . A method of treating a disease comprising administering a therapeutically effective amount of the molecule of  claim 29  to an individual in need thereof. 
     
     
         43 . The method of  claim 42 , wherein the disease is one that can be treated by regulating the Stat3 pathway or genes under control of Stat3. 
     
     
         44 . The method of  claim 42 , wherein the disease is selected from the group consisting of cancer, an infectious disease, an autoimmune disease, a disease due to excessive angiogenesis and a disease benefits from increased angiogenesis.