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 a targeting moiety covalently bound to a first oligonucleotide through a first spacer, wherein:
(i) said first oligonucleotide is hybridized to a second complementary oligonucleotide to form a multifunctional linker, wherein said second complementary oligonucleotide is covalently bound to a first active agent through a second spacer, wherein said second complementary oligonucleotide and the complementary portion of said first oligonucleotide comprise 2′-fluoro, 2-O-methyl or locked nucleic acid; and
(ii) said first spacer and said second spacer consist of one or more C3 spacers.
2. The molecule of claim 1 , wherein said first active agent is covalently bound to the 5′ end of said second oligonucleotide through said second spacer.
3. The molecule of claim 2 , wherein a second active agent is covalently bound to the 3′ end of said second oligonucleotide through a third spacer.
4. The molecule of claim 3 , wherein a third active agent is covalently bound to said first oligonucleotide through a fourth spacer.
5. The molecule of claim 4 , wherein said third spacer and said fourth spacer consist of one or more C3 spacers.
6. The molecule of claim 5 , wherein said third active agent is covalently bound to the 3′ end of said first oligonucleotide through said fourth spacer.
7. The molecule of claim 6 , wherein said targeting moiety is covalently bound to the 5′ end of said first oligonucleotide through said first spacer.
8. The molecule of claim 1 , wherein said targeting moiety is capable of delivering the molecule to a cell of interest.
9. The molecule of claim 8 , wherein said targeting moiety is a CpG oligodeoxynucleotide or an aptamer.
10. The molecule of claim 8 , wherein said targeting moiety is a Toll-like receptor ligand.
11. The molecule of claim 4 , wherein said first active agent, said second active agent and said third active agent are independently a double stranded RNA, a small molecule drug or a peptide.
12. The molecule of claim 11 , wherein said double stranded RNA is an siRNA.
13. The molecule of claim 4 , wherein said first active agent, said second active agent and said third active agent are independently capable of treating a disease.
14. The molecule of claim 13 , 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.