Methods and compositions for the treatment of cancer or other diseases
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. A molecule comprising:
(i) a targeting moiety covalently bound to a first oligonucleotide through a linker, wherein said linker comprises one or more C3 spacers; and
(ii) a second complementary oligonucleotide hybridized to said first oligonucleotide to form a double-stranded RNA bound to said targeting moiety.
2. The molecule of claim 1 , wherein said targeting moiety is covalently bound to the 5′ end of said first oligonucleotide through said linker.
3. The molecule of claim 2 , wherein said targeting moiety is a CpG oligodeoxynucleotide or an aptamer.
4. The molecule of claim 3 , wherein said targeting moiety is a phosphorothioated oligodeoxynucleotide.
5. The molecule of claim 4 , wherein said oligodeoxynucleotide is about 8 to 40 base pairs in length.
6. The molecule of claim 5 , wherein said targeting moiety is a Toll-like receptor ligand.
7. The molecule of claim 6 , wherein said targeting moiety is capable of delivering the molecule to a cell of interest.
8. The molecule of claim 7 , 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.
9. The molecule of claim 1 , wherein said second complementary oligonucleotide comprises 2′-fluoro, 2-O-methyl or locked nucleic acid.
10. The molecule of claim 9 , wherein said double-stranded RNA is a siRNA.
11. The molecule of claim 10 , wherein said double-stranded RNA is about 19 to 30 base pairs in length.
12. The molecule of claim 11 , wherein said double-stranded RNA comprises one or more deoxynucleotides.
13. A pharmaceutical composition comprising the molecule of claim 1 and a pharmaceutically acceptable carrier.
14. A method of treating a disease comprising administering a therapeutically effective amount of the molecule of claim 1 to an individual in need thereof.
15. The method of claim 14 , wherein the disease is one that can be treated by regulating the Stat3 pathway or genes under control of Stat3.
16. The method of claim 14 or 15 , 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.