IP Library › Granted Patent US 7,704,954
Granted Patent B2
US 7,704,954 · App. 10/838,135 · Granted Apr 27, 2010

Method and carrier complexes for delivering molecules to cells

Assignee: Cornell Research Foundation, Inc.
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Quick Facts
Patent No.
US 7,704,954
App. No.
10/838,135
Granted
Apr 27, 2010
Kind
B2
Abstract

The invention relates to carrier complexes and methods for delivering molecules to cells. The carrier complexes comprises a molecule and an aromatic cationic peptide in accordance with the invention. In one embodiment, the method for delivering a molecule to a cell comprises contacting the cell with a carrier complex. In another embodiment, the method for delivering a molecule to a cell comprises contacting the cell with a molecule and an aromatic cationic peptide.

Claims (101)

1. A method for delivering a molecule to a cell, the method comprising contacting the cell with a carrier complex, wherein the carrier complex comprises the molecule conjugated to an aromatic cationic peptide, wherein the aromatic cationic peptide is selected from the group consisting of:

Tyr- D -Arg-Phe-Lys-NH 2 (DALDA),

2′,6′-Dmt- D -Arg-Phe-Lys-NH 2 (Dmt 1 -DALDA),

Phe- D -Arg-Phe-Lys-NH 2 (Phe 1 -DALDA),

D -Arg-2′,6′Dmt-Lys-Phe-NH 2 , and

2′,6′-Dmp- D -Arg-Phe-Lys-NH 2 (Dmp 1 -DALDA); and

wherein the molecule is selected from the group consisting of: a polynucleotide, a polyamino acid, a cytotoxic agent, an antibiotic, an antioxidant, a growth factor, and a cytokine.

2. A method according to claim 1 , wherein the peptide has the formula Tyr- D -Arg-Phe-Lys-NH 2 (DALDA).

3. A method according to claim 1 , wherein the peptide has the formula 2′,6′-Dmt- D -Arg-Phe-Lys-NH 2 (Dmt 1 -DALDA).

4. A method according to claim 1 , wherein the peptide has the formula Phe- D -Arg-Phe-Lys-NH 2 (Phe 1 -DALDA).

5. A method according to claim 1 , wherein the peptide has the formula D -Arg-2′,6′Dmt-Lys-Phe-NH 2 .

6. A method according to claim 1 , wherein the peptide has the formula 2′,6′-Dmp- D -Arg-Phe-Lys-NH 2 (Dmp 1 -DALDA).

7. A method according to claim 1 , wherein the molecule is an antibiotic.

8. A method according to claim 1 wherein the molecule is a cytotoxic agent.

9. A method according to claim 8 , wherein the cytotoxic agent is doxorubicin.

10. A method according to claim 8 , wherein the cytotoxic agent is adriamycin.

11. A method according to claim 1 , wherein the molecule is an antioxidant.

12. A method according to claim 11 wherein the antioxidant is vitamin E.

13. A method according to claim 11 , wherein the antioxidant is vitamin C.

14. A method according to claim 11 , wherein the antioxidant is beta carotene.

15. A method according to claim 1 , wherein the molecule is a polyamino acid.

16. A method according to claim 15 , wherein the polyamino acid is an endogenous peptide or protein.

17. A method according to claim 15 , wherein the polyamino acid is an enzyme.

18. A method according to claim 15 , wherein the polyamino acid is an antibody.

19. A method according to claim 1 , wherein the growth factor is a neurotrophic growth factor.

20. A method according to claim 15 , wherein the molecule is a cytokine.

21. A method according to claim 15 , wherein the molecule is a polynucleotide.

22. A method according to claim 21 , wherein the polynucleotide is an oligonucleotide.

23. A method according to claim 22 , wherein the oligonucleotide is RNA.

24. A method according to claim 23 , wherein the RNA is double-stranded RNA.

25. A method according to claim 24 , wherein the double-stranded RNA is siRNA.

26. A method according to claim 22 , wherein the oligonucleotide is DNA.

27. A method according to claim 22 , wherein the oligonucleotide is single-stranded RNA.

28. A method according to claim 27 , wherein the single-stranded RNA is messenger RNA (mRNA).

29. A method according to claim 22 , wherein the oligonucleotide is a ribozyme.

30. A method according to claim 22 , wherein the oligonucleotide is an anti-sense RNA.

31. A method according to claim 22 , wherein the oligonucleotide is an external guide sequence for a ribozyme.

32. A method according to claim 22 , wherein the oligonucleotide is an RNA decoy.

33. A method according to claim 1 , wherein the cell is a bacterial cell.

34. A method according to claim 1 , wherein the cell is a plant cell.

35. A method according to claim 1 , wherein the cell is an animal cell.

36. A method according to claim 35 , wherein the animal cell is a mammalian cell.

37. A method according to claim 35 , wherein the cell is a neuronal cell.

38. A method according to claim 35 , wherein the cell is a renal epithelial cell.

39. A method according to claim 35 , wherein the cell is an intestinal epithelial cell.

40. A method according to claim 35 , wherein the cell is a vascular endothelial cell.

41. A method according to claim 35 , wherein the endothelial cell is a blood-brain barrier endothelial cell.

42. A method according to claim 35 , wherein the cell is a glial cell.

43. A method according to claim 35 , wherein the cell is a hepatocyte.

44. A method according to claim 1 , wherein the aromatic-cationic peptide comprises a linker.

45. A method according to claim 1 , wherein the molecule comprises a linker.

46. A method according to claim 1 , wherein the molecule and aromatic cationic peptide are chemically bonded.

47. A carrier complex comprising a molecule conjugated to an aromatic cationic peptide, wherein the aromatic cationic peptide is selected from the group consisting of:

Tyr- D -Arg-Phe-Lys-NH 2 (DALDA),

2′,6′-Dmt- D -Arg-Phe-Lys-NH 2 (Dmt 1 -DALDA),

Phe- D -Arg-Phe-Lys-NH 2 (Phe 1 -DALDA),

D -Arg-2′,6′Dmt-Lys-Phe-NH 2 , and

2′,6′-Dmp- D -Arg-Phe-Lys-NH 2 (Dmp 1 -DALDA); and

wherein the molecule is selected from the group consisting of: a polynucleotide, a polyamino acid, a cytotoxic agent, an antibiotic, an antioxidant, a growth factor, and a cytokine.

48. A carrier complex according to claim 47 , wherein the peptide has the formula Tyr- D -Arg-Phe-Lys-NH 2 (DALDA).

49. A carrier complex according to claim 47 , wherein the peptide has the formula 2′,6′-Dmt- D -Arg-Phe-Lys-NH 2 (Dmt 1 -DALDA).

50. A carrier complex according to claim 47 , wherein the peptide has the formula Phe- D -Arg-Phe-Lys-NH 2 (Phe 1 -DALDA).

51. A carrier complex according to claim 47 , wherein the peptide has the formula D -Arg-2′,6′Dmt-Lys-Phe-NH 2 .

52. A carrier complex according to claim 47 , wherein the peptide has the formula 2′,6′-Dmp- D -Arg-Phe-Lys-NH 2 (Dmp 1 -DALDA).

53. A carrier complex according to claim 47 , wherein the molecule is an antibiotic.

54. A carrier complex according to claim 47 , wherein the molecule is a cytotoxic agent.

55. A carrier complex according to claim 54 , wherein the cytotoxic agent is doxorubicin.

56. A carrier complex according to claim 54 , wherein the cytotoxic agent is adriamycin.

57. A carrier complex according to claim 47 , wherein the molecule is an antioxidant.

58. A carrier complex according to claim 57 , wherein the antioxidant is vitamin E.

59. A carrier complex according to claim 57 , wherein the antioxidant is vitamin C.

60. A carrier complex according to claim 57 , wherein the antioxidant is beta carotene.

61. A carrier complex according to claim 47 , wherein the polyamino acid is an endogenous peptide or protein.

62. A carrier complex according to claim 47 , wherein the polyamino acid is an enzyme.

63. A carrier complex according to claim 47 , wherein the polyamino acid is an antibody.

64. A carrier complex according to claim 47 , wherein the growth factor is a neurotrophic growth factor.

65. A carrier complex according to claim 47 , wherein the molecule is a cytokine.

66. A carrier complex according to claim 47 , wherein the molecule is a polynucleotide.

67. A carrier complex according to claim 66 , wherein the polynucleotide is an oligonucleotide.

68. A carrier complex according to claim 67 , wherein the oligonucleotide is RNA.

69. A carrier complex according to claim 68 wherein the RNA is double-stranded RNA.

70. A carrier complex according to claim 69 , wherein the double-stranded RNA is siRNA.

71. A carrier complex according to claim 67 , wherein the oligonucleotide is DNA.

72. A carrier complex according to claim 67 , wherein the oligonucleotide is single-stranded RNA.

73. A carrier complex according to claim 72 , wherein the single-stranded RNA is messenger RNA (mRNA).

74. A carrier complex according to claim 67 , wherein the oligonucleotide is a ribozyme.

75. A carrier complex according to claim 67 , wherein the oligonucleotide is an anti-sense RNA.

76. A carrier complex according to claim 67 , wherein the oligonucleotide is an external guide sequence for a ribozyme.

77. A carrier complex according to claim 67 , wherein the oligonucleotide is an RNA decoy.

78. A carrier complex according to claim 47 , wherein the molecule is a polyamino acid.

79. A carrier complex according to claim 47 , wherein the aromatic cationic peptide comprises a linker.

80. A carrier complex according to claim 47 , wherein the molecule comprises a linker.

81. A carrier complex according to claim 47 , wherein the molecule and aromatic cationic peptide are chemically bonded.

82. A method for delivering a molecule to a cell, the method comprising contacting the cell with a molecule conjugated to an aromatic cationic peptide, wherein the aromatic cationic peptide is selected from the group consisting of:

Tyr- D -Arg-Phe-Lys-NH 2 (DALDA),

2′,6′-Dmt- D -Arg-Phe-Lys-NH 2 (Dmt 1 -DALDA),

Phe- D -Arg-Phe-Lys-NH 2 (Phe 1 -DALDA),

D -Arg-2′,6′Dmt-Lys-Phe-NH 2 , and

2′,6′-Dmp- D -Arg-Phe-Lys-NH 2 (Dmp 1 -DALDA); and

wherein the molecule is selected from the group consisting of: a polynucleotide, a polyamino acid, a cytotoxic agent, an antibiotic, an antioxidant, a growth factor, and a cytokine.

83. A method according to claim 82 , wherein the molecule and aromatic cationic peptide are chemically bonded.

Assignments (2)
EXECUTIVE ORDER 9424, CONFIRMATORY LICENSE Recorded Aug 15, 2008
From: CORNELL UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 021397/0892 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 22, 2004
From: SZETO, HAZEL H.; ZHAO, KESHENG; ROBERTSON, HUGH D.; BIRK, ALEX V.
To: CORNELL RESEARCH FOUNDATION, INC.
Reel/Frame 016006/0084 →
Continuity (2)
Provisional Application 6046751600 · May 1, 2003
Related Publication 20050158373A1 · Jul 21, 2005