Therapeutic anti-cancer DNA

• US 20050215507A1
• Filed: 03/04/2005
• Published: 09/29/2005
• Est. Priority Date: 03/04/2004
• Status: Abandoned Application

• Current Assignee: Massachusetts Institute of Technology
• Original Assignee: Lankenau Institute for Medical Research, Massachusetts Institute of Technology
• Inventors: Sawicki, Janet, Anderson, Daniel Griffith, Langer, Robert, Peng, Weidan
• Application Number:
  US11/074,323
• Publication Number:
  US 20050215507A1
• Time in Patent Office: Days
• US Class Current: 514/44.R
• CPC Class Codes: A61K 48/0058 Nucleic acids adapted for tissue specific expression, e.g. having tissue specific promoters as part of a contruct
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 15/88 using microencapsulation, e.g. using amphiphile liposome vesicle
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2800/30 Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT
• CPC Class Codes: C12N 2830/008 cell type or tissue specific enhancer/promoter combination
• CPC Class Codes: C12N 2830/15 chimeric enhancer/promoter combination

Abstract

Aspects of the invention relate to nucleic acids molecules that are useful for specifically destroying selected cells, tissues, or organs. Aspects of the invention are useful for treating diseases (e.g., cancer) that affect specific cells, tissues, or organs.

Claims

1. A composition comprising:

a first nucleic acid comprising a first promoter operably joined to a sequence encoding a recombinase,

a second nucleic acid comprising a second promoter, a sequence encoding a toxin, and at least one target sequence that is recognized by the recombinase,

wherein the second promoter and the sequence encoding the toxin are arranged such they are only operably joined if the recombinase acts on the at least one target sequence, and wherein the first promoter is a tissue specific promoter that is selectively active in non-vital tissue.

2. The composition of claim 1, wherein the first promoter is selectively active in a non-vital organ.

3. The composition of claim 2, wherein the non-vital organ is breast, thyroid, ovary, or testes.

4. The composition of claim 2, wherein the non-vital organ is a prostate.

5. The composition of claim 1, wherein the first promoter is a modified promoter.

6. The composition of claim 1, wherein the first nucleic acid further comprises an enhancer element.

7. The composition of claim 1, wherein the first promoter is a modified prostate specific promoter.

8. The composition of claim 7, wherein the modified prostate specific promoter is a modified PSA promoter.

9. The composition of claim 8, wherein the modified PSA promoter is PSA-BC.

10. The composition of claim 1, wherein the second promoter is a tissue-specific promoter.

11. The composition of claim 1, wherein the second promoter is not tissue-specific.

12. The composition of claim 1, wherein the second promoter is an xenogeneic promoter.

13. The composition of claim 12, wherein the xenogeneic promoter is a mammalian promoter.

14. The composition of claim 12, wherein the xenogeneic promoter is a viral promoter.

15. The composition of claim 1, wherein the toxin is a protein.

16. The composition of claim 1, wherein the toxin is an enzyme.

17. The composition of claim 15, wherein the protein is a modified natural protein.

18. The composition of claim 15, wherein the protein is the A chain of diphtheria toxin.

19. The composition of claim 1, wherein the first and second nucleic acids are covalently linked.

20. The composition of claim 19, wherein the first and second nucleic acids are comprised by a single linear nucleic acid.

21. The composition of claim 19, wherein the first and second nucleic acids are comprised by a single circular nucleic acid.

22. A nucleic acid delivery preparation comprising the nucleic acid of claim 1 and a cationic polymer.

24. A method of targeting a toxin to a non-vital cell type, the method comprising contacting a cell with a composition of claim 1, wherein the first promoter is selectively active in the cell.

25. The method of claim 24, wherein the non-vital cell type is a prostate epithelial cell.

33. A method of treating cancer comprising, administering a composition of claim 1 to a subject that has cancer.

39. The composition of claim 1, wherein the recombinase is Flp recombinase.

40. A nucleic acid delivery preparation of claim 22, wherein the cationic polymer is a poly(β

-aminoester).

41. The nucleic acid delivery preparation of claim 40, wherein the cationic polymer is C32.

23. A nucleic acid delivery preparation comprising a cationic polymer and a nucleic acid composition comprising:

a first nucleic acid comprising a first promoter operably joined to a sequence encoding a recombinase,

a second nucleic acid comprising a second promoter, a sequence encoding a toxin, and at least one target sequence that is recognized by the recombinase,

wherein the second promoter and the sequence encoding the toxin are arranged such they are only operably joined if the recombinase acts on the at least one target sequence.

26. A method of targeting a toxin to a specific cell type, the method comprising contacting a cell of a specific cell type with the nucleic acid delivery preparation of claim 23, wherein the first promoter is selectively active in the specific cell type.

34. A method of treating cancer comprising, administering a nucleic acid delivery preparation of claim 23 to a subject that has cancer.

27. A method of targeting a toxin to a diseased cell type, the method comprising administering to a subject having a disease a nucleic acid composition comprising:

a first nucleic acid comprising a first promoter operably joined to a sequence encoding a recombinase,

a second nucleic acid comprising a second promoter, a sequence encoding a toxin, and at least one target sequence that is recognized by the recombinase,

wherein the second promoter and the sequence encoding the toxin are arranged such they are only operably joined if the recombinase acts on the at least one target sequence,

wherein the first promoter is selectively active in a population of cells comprising diseased cells, and

wherein the nucleic acid composition is administered non-virally.

28. The method of claim 27, wherein the nucleic acid composition is a plasmid.

29. The method of claim 27, wherein the nucleic acid composition is administered in combination with a cationic polymer.

30. The method of claim 27, wherein the first promoter is selectively active in cancer cells.

31. The method of claim 27, wherein the first promoter is tissue specific.

32. The method of claim 27, wherein the disease is cancer.

35-38. -38. (canceled)