Nucleic acid formulations for gene delivery and methods of use

1. A formulation for delivery to a cell of a nucleic acid encoding a protein, comprising said nucleic acid and an anionic polymer selected from the group consisting of poly glutamic acid, poly aspartic acid, poly galacturonic acid, poly vinyl sulfate, a copolymer consisting of glutamic acid and aspartic acid, and salts thereof, wherein the anionic polymer is non-encapsulating and enhances delivery of the nucleic acid to the cell compared to delivery of the nucleic acid without the polymer, and wherein the formulation does not contain a cationic polymer.

2. The formulation of claim 1 wherein the anionic polymer is selected from the group consisting of poly-L-glutamic acid and poly aspartic acid, and salts thereof.

3. The formulation of claim 2 , wherein the anionic polymer is characterized by a molecular weight in the range from 2,000 to 100,000 Daltons.

4. The formulation of claim 3 , wherein the anionic polymer is characterized by a molecular weight in the range from about 15,000 to about 50,000 Daltons.

5. The formulation of claim 3 , wherein the anionic polymer is characterized by a molecular weight in the range from about 2,000 to about 15,000 Daltons.

6. The formulation of claim 3 , wherein the anionic polymer acid is characterized by a molecular weight in the range from about 50,000 to about 100,000 Daltons.

7. The formulation of claim 1 , wherein the anionic polymer is formulated with the nucleic acid molecule at an anionic polymer concentration ranging from 1 to 12 mg/ml.

8. The formulation of claim 7 , wherein the anionic polymer thereof is formulated with the nucleic acid molecule at an anionic polymer concentration of about 2 to about 6 mg/ml.

9. The formulation of claim 1 , wherein the formulation is isotonic.

10. The formulation of claim 1 , wherein the anionic polymer enhances delivery of the nucleic acid to the cell in vivo.

11. The formulation of claim 10 , wherein the anionic polymer enhances delivery of the nucleic acid to a cell in a muscle tissue in vivo.

12. The formulation of claim 10 , wherein the anionic polymer enhances delivery of the nucleic acid to multiple cells in vivo.

13. The formulation of claim 1 , wherein the anionic polymer confers stability to the nucleic acid during storage conditions selected from the group consisting of liquid storage, lyophilization, and freezing.

14. The formulation of claim 1 , wherein the nucleic acid comprises a sequence encoding a protein selected from the group consisting of growth hormones, growth factors, cytokines, clotting factors, antigens, and antigenic factors.

15. The formulation of claim 14 , wherein the cytokine is an interferon.

16. The formulation of claim 1 , further comprising a buffer suitable for internal administration.

17. The formulation of claim 1 , wherein the poly glutamic acid is a poly-L-glutamic acid, or salt thereof, at a concentration of about 6 mg/ml and the formulation further comprises about 150 mM NaCl.

18. The formulation of claim 17 , wherein the nucleic acid is present in the formulation at about 1 mg/ml.

19. The formulation of claim 17 or 18 , further comprising a Tris buffer at a concentration ranging from about 5 mM to about 10 mM.

20. A lyophilized nucleic acid formulation comprising a nucleic acid encoding a protein and an anionic polymer selected from the group consisting of poly glutamic acid, poly aspartic acid, poly galacturonic acid, poly vinyl sulfate, a copolymer consisting of glutamic acid and aspartic acid, and salts thereof, wherein the anionic polymer is non-encapsulating and the formulation does not contain a cationic polymer.

21. The formulation of claim 20 , wherein the poly glutamic acid is a poly-L-glutamic acid or salt thereof.

22. The formulation of claim 21 , wherein the salt of poly-L-glutamic acid is a sodium salt and is present in the formulation at a concentration of 1 to 12 mg/ml prior to lyophilization.

23. The formulation of claim 22 , wherein the sodium salt of poly-L-glutamic acid is present in the formulation at a concentration of about 6 mg/ml prior to lyophilization.

24. The formulation of claim 1 wherein said protein is a therapeutic protein.

25. The formulation of claim 1 wherein the anionic polymer is a poly-L-gluta mate or a salt thereof.

26. The formulation of claim 1 wherein the nucleic acid encodes a cytokine.

27. A pharmaceutical composition for increasing a blood level of a therapeutic protein comprising a plasmid vector encoding the therapeutic protein, an anionic polymer selected from the group consisting of poly glutamic acid, poly aspartic acid, poly galacturonic acid, poly vinyl sulfate, a copolymer consisting of glutamic acid and aspartic acid, and salts thereof, wherein the anionic polymer is non-encapsulating, and the formulation does not contain a cationic polymer.

28. The pharmaceutical composition of claim 27 , wherein the anionic polymer enhances transfection in conjunction with electroporation in vivo.

29. The pharmaceutical composition of claim 28 wherein the poly glutamic acid is poly-L-glutamic acid or a salt thereof.

30. The pharmaceutical composition of claim 27 , wherein the therapeutic protein is selected from the group consisting of a clotting factor, a growth factor; and a cytokine.

31. The pharmaceutical composition of claim 27 wherein the therapeutic protein is selected from the group consisting of Factor IX, erythropoietin, and interferon alpha.

32. A stabilized pharmaceutical composition for increasing a blood level of a therapeutic protein, comprising a non-viral vector encoding the therapeutic protein and an anionic polymer selected from the group consisting of poly glutamic acid, poly aspartic acid, poly galacturonic acid, poly vinyl sulfate, a copolymer consisting of glutamic acid and aspartic acid, and salts thereof, wherein the anionic polymer is non-encapsulating, and the formulation does not contain a cationic polymer.

33. The stabilized pharmaceutical composition of claim 32 , wherein the anionic copolymer is a poly-L-glutamate or a salt thereof.

34. The formulation of claim 14 , wherein the clotting factor is a Factor IX.

35. The formulation of claim 14 , wherein the growth factor is an erythropoietin.