Nanogene therapy for cell proliferation disorders

• US 20050266093A1
• Filed: 04/27/2005
• Published: 12/01/2005
• Est. Priority Date: 04/27/2004
• Status: Abandoned Application

• Current Assignee: University of South Florida (State University System of Florida)
• Original Assignee: University of South Florida (State University System of Florida)
• Inventors: Mohapatra, Shyam S.
• Application Number:
  US11/117,169
• Publication Number:
  US 20050266093A1
• Time in Patent Office: Days
• US Class Current: 424/492
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 38/212 IFN-alpha
• CPC Class Codes: A61K 38/215 IFN-beta
• CPC Class Codes: A61K 38/217 IFN-gamma
• CPC Class Codes: A61K 38/53 Ligases (6)
• CPC Class Codes: A61K 48/0025 wherein the non-active part clearly interacts with the delivered nucleic acid
• CPC Class Codes: A61K 48/0075 characterised by an aspect of the delivery route, e.g. oral, subcutaneous
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/5161 Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/57 IFN-gamma
• CPC Class Codes: C12N 15/88 using microencapsulation, e.g. using amphiphile liposome vesicle

Abstract

The present invention concerns particles comprising a chitin component, such as chitosan or a derivative thereof, associated with a polynucleotide encoding an interferon (IFN) molecule, 2-5′ oligoadenylate synthetase (2-5 AS), or a combination thereof. Preferably, the chitin component comprises chitosan or a derivative thereof. The particles of the invention are useful for delivery and expression of the interferon-encoding and/or 2-5 AS-encoding polynucleotide within a host in vitro or in vivo. The invention further concerns pharmaceutical compositions comprising particles of the invention and a pharmaceutically acceptable carrier, and a method for producing particles of the present invention. The present invention further pertains to a method of inducing apoptosis in a cancer cell, such as a lung cancer cell, by contacting a target cancer cell in vitro or in vivo with an effective amount of particles of the invention. In one embodiment, a therapeutically effective amount of particles are administered to target cancer cells within a patient in vivo, for treatment of cancer, such as lung cancer. The particles and therapeutic methods of the invention provide anti-metastatic and anti-cancer therapeutics for cancer patients, particularly lung cancer patients.

Claims

1. A method for treating a cell proliferation disorder in a subject, comprising administering a therapeutically effective amount of particles to the subject, wherein the particles comprise:

a polynucleotide encoding an interferon, an interferon-inducible molecule, or both; and

a chitin-containing component associated with the polynucleotide, wherein the polynucleotide is expressed in the subject and cell proliferation is reduced.

2. The method of claim 1, wherein the interferon is selected from the group consisting of alpha interferon, beta interferon, gamma interferon, omega interferon, and lambda interferon, or a biologically active fragment or derivative thereof.

3. The method of claim 1, wherein the interferon is gamma interferon.

4. The method of claim 1, wherein the interferon is a hybrid interferon.

5. The method of claim 1, wherein the interferon inducible molecule comprises interferon regulatory factor-1 (IRF-1).

6. The method of claim 1, wherein the interferon-inducible molecule comprises 2′

-5′

oligoadenylate synthetase, interferon regulatory factor-1 (IRF-1), or both.

7. The method of claim 1, wherein the interferon-inducible molecule comprises a catalytically active subunit of 2′

-5′

oligoadenylate synthetase selected from the group consisting of p40, p69, and p100 subunit.

8. The method of claim 1, wherein the 2′

-5′

oligoadenylate synthetase comprises at least one splice variant selected from the group consisting of 40 kDa, 42 kDa, 46 kDa, 69 kDa, and 71 kDa.

9. The method of claim 1, wherein the chitin-containing component comprises chitosan or a chitosan derivative.

10. The method of claim 1, wherein the particles further comprise a lipid component associated with the chitin-containing component and the polynucleotide.

11. The method of claim 1, wherein the cell proliferation disorder is a cancer of the respiratory tract.

12. The method of claim 1, wherein the cell proliferation disorder is lung cancer.

13. The method of claim 1, wherein the particles are administered to the subject via a mucosal route.

14. The method of claim 1, wherein the particles are administered to the subject intranasally.

15. The method of claim 1, wherein the particles are administered to the subject as a spray, drops, powder, gel, or a combination of two or more of the foregoing.

16. The method of claim 1, wherein the subject is human.

17. The method of claim 1, wherein the subject is suffering from a cell proliferation disorder.

18. The method of claim 1, wherein the subject has been diagnosed with the cell proliferation disorder prior to said administering.

19. A method of inducing apoptosis in a cancer cell, comprising contacting a target cancer cell in vitro or in vivo with an effective amount of particles comprising:

a polynucleotide encoding an interferon, an interferon-inducible molecule, or both; and

a chitin-containing component associated with the polynucleotide, wherein the polynucleotide is expressed in the cancer cell and apoptosis is induced.

20. The method of claim 19, wherein the interferon is selected from the group consisting of alpha interferon, beta interferon, gamma interferon, omega interferon, and lambda interferon, or a biologically active fragment or derivative thereof.

21. The method of claim 19, wherein the interferon-inducible molecule comprises 2′

-5′

oligoadenylate synthetase, interferon regulatory factor-1 (IRF-1), or both.

22. The method of claim 19, wherein the cancer cell is a respiratory epithelial cell.

23. A particle comprising a polynucleotide encoding an interferon, an interferon-inducible molecule, or both;

and a chitin-containing component associated with the polynucleotide.

24. The particle of claim 23, wherein said chitin-containing component comprises chitosan or a chitosan derivative.

25. The particle of claim 23, wherein said particle further comprises a lipid component associated with the chitin-containing component and the polynucleotide.

26. The particle of claim 23, wherein said particle comprises a polynucleotide encoding said interferon and said interferon-inducible molecule.

27. The particle of claim 23, wherein said particle comprises a polynucleotide encoding said interferon and 2′

-5′

oligoadenylate synthetase.

28. The particle of claim 23, wherein said particle comprises a polynucleotide encoding said interferon and interferon regulatory factor-1 (IRF-1).

29. The particle of claim 23, wherein said particle comprises a polynucleotide encoding 2′

-5′

oligoadenylate synthetase and interferon regulatory factor-1 (IRF-1).

30. The particle of claim 23, wherein said particle comprises a polynucleotide encoding said interferon, 2′

-5′

oligoadenylate synthetase, and interferon regulatory factor-1 (IRF-1).

31. The particle of claim 23, wherein said polynucleotide comprises one or more nucleotide sequences selected from the group consisting of SEQ ID NOs:

1, 3, 5, 7, 9, 11, 13, 14, 15, 16, 17, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, and 31.