Methods and compositions related to targeting wounds, regenerating tissue, and tumors
View Patent ↗Disclosed are compositions and methods useful for targeting regenerating tissue, wounds, and tumors. The compositions and methods are based on peptide sequences that selectively bind to and home to regenerating tissue, wound sites, and tumors in animals. The disclosed targeting is useful for delivering therapeutic and detectable agents to regenerating tissue, wound sites, and tumors in animals.
1. A method for healing wounds and suppressing scar formation, the method comprising administering to a subject a conjugate comprising a moiety and a peptide, wherein the peptide comprises an amino acid segment comprising the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 having one or more conservative amino acid substitutions.
2. The method of claim 1 , wherein the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO: 2 has two or more conservative amino acid substitutions.
3. The method of claim 1 , wherein the amino acid segment comprises the amino acid sequence of SEQ ID NO: 1 or SEQ ID NO:2.
4. The method of claim 1 , wherein the peptide has a length of less than 100 residues.
5. The method of claim 1 , wherein the peptide has a length of less than 50 residues.
6. The method of claim 1 , wherein the peptide has a length of less than 20 residues.
7. The method of claim 1 , wherein the amino acid segment is cyclic.
8. The method of claim 7 , wherein the amino acid segment is cyclized via a disulfide bond.
9. The method of claim 1 , wherein the peptide selectively homes to regenerating tissue.
10. The method of claim 9 , wherein the regenerating tissue is at the site of an injury.
11. The method of claim 9 , wherein the regenerating tissue is at a surgical site.
12. The method of claim 1 , wherein the peptide selectively homes to a site of inflammation.
13. The method of claim 1 , wherein the peptide selectively homes to a site of arthritis.
14. The method of claim 1 , wherein the peptide consists of the amino acid segment.
15. The method of claim 1 , wherein the moiety is linked to the peptide.
16. The method of claim 1 , wherein the peptide selectively interacts with regenerating tissue.
17. The method of claim 1 , wherein the peptide selectively interacts with tissue at the site of inflammation.
18. The method of claim 1 , wherein the peptide selectively interacts tissue at a site of arthritis.
19. The method of claim 1 , wherein the moiety is a an anti-angiogenic agent, a pro-angiogenic agent, a cytotoxic agent, an anti-inflammatory agent, an anti-arthritic agent, a polypeptide, a nucleic acid molecule, a small molecule, a fluorophore, fluorescein, rhodamine, a radionuclide, indium-Ill, technetium-99, carbon-II, carbon-13, or a combination.
20. The method of claim 1 , wherein the moiety is a therapeutic agent.
21. The method of claim 20 , wherein the therapeutic agent is decorin.
22. The method of claim 1 , wherein the moiety is a detectable agent.
23. The method of claim 1 , wherein the conjugate comprises a virus.
24. The method of claim 23 , wherein the conjugate comprises a phage.
25. The method of claim 1 , wherein the moiety is directed to regenerating tissue.
26. The method of claim 25 , wherein the moiety is directed to a site of injury.
27. The method of claim 25 , wherein the moiety is directed to a surgical site.
28. The method of claim 1 , wherein the moiety is directed to a site of inflammation.
29. The method of claim 26 , wherein the conjugate has a therapeutic effect.
30. The method of claim 29 , wherein the therapeutic effect comprises a reduction in inflammation, an increase in speed of wound healing, reduction in amounts of scar tissue, decrease in pain, decrease in swelling, or decrease in necrosis.
31. The method of claim 26 , wherein the subject has one or more site to be targeted, wherein the moiety is directed to one or more of the sites to be targeted.
32. The method of claim 1 , wherein the amino acid segment consists of the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2, or the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2 having one, two, or three consecutive amino acid substitutions.
33. The method of claim 32 , wherein the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2 has one or two conservative amino acid substitutions.
34. The method of claim 33 , wherein the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2 has one conservative amino acid substitution.
35. The method of claim 32 , wherein the amino acid segment consists of the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2.
36. The method of claim 1 , wherein the peptide is fused to at least one heterologous moiety.
37. The method of claim 1 , wherein the peptide is part of a chimeric protein.
38. The method of claim 1 , wherein the peptide consists of an amino acid segment, wherein the amino acid segment consists of the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2, or the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2 having one or more conservative amino acid substitutions, wherein the peptide has a length of less than 20 residues.
39. The method of claim 1 , wherein the peptide comprises an amino acid segment comprising the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2, or the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2 having one, two, or three conservative substitutions.
40. The method of claim 39 , wherein the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2 has one or two conservative amino acid substitutions.
41. The method of claim 39 , wherein the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2 has one conservative amino acid substitution.
42. The method of claim 39 , wherein the amino acid segment consists of the amino acid sequence.
43. The method of claim 42 , wherein the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2 has one or two conservative amino acid substitutions.
44. The method of claim 43 , wherein the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2 has one conservative amino acid substitution.
45. The method of claim 42 , wherein the amino acid segment consists of the amino acid sequence of SEQ ID NO:1 or SEQ ID NO:2.
46. The method of claim 39 , wherein the peptide consists of the amino acid segment.
47. The method of claim 1 , wherein the amino acid segment comprises the amino acid sequence of SEQ ID NO:2, or the amino acid sequence of SEQ ID NO:2 having one or more conservative amino acid substitutions, wherein the peptide has a length of less than 20 residues.
48. The method of claim 1 , wherein the amino acid segment comprises the amino acid sequence of SEQ ID NO:2, or the amino acid sequence of SEQ ID NO:2 having one or more conservative amino acid substitutions, wherein the peptide has a length of less than 100 residues, wherein the amino acid segment is cyclic.
49. The method of claim 1 , wherein the amino acid segment comprises the amino acid sequence of SEQ ID NO:2, or the amino acid sequence of SEQ ID NO:2 having one or more conservative amino acid substitutions, wherein the peptide has a length of less than 100 residues, wherein the peptide is part of a chimeric protein.
50. The method of claim 1 , wherein the amino acid segment comprises the amino acid sequence of SEQ ID NO:2, or the amino acid sequence of SEQ ID NO:2 having one or more conservative amino acid substitutions, wherein the peptide has a length of less than 100 residues.
51. The method of claim 1 , wherein the amino acid sequence of SEQ ID NO:1 has one conservative amino acid substitution.
52. The method of claim 1 , wherein the amino acid segment comprises the amino acid sequence of SEQ ID NO:1.
53. The method of claim 1 , wherein the amino acid segment comprises the amino acid sequence of SEQ ID NO:2, wherein the peptide has a length of less than 70 residues.
54. The method of claim 1 , wherein the amino acid segment comprises the amino acid sequence of SEQ ID NO:1 or the amino acid sequence of SEQ ID NO:1 having one or more conservative amino acid substitutions, wherein the peptide has a length of less than 50 residues.
55. The method of claim 1 , wherein the amino acid segment comprises the amino acid sequence of SEQ ID NO:2 or the amino acid sequence of SEQ ID NO:2 having one or more conservative amino acid substitutions, wherein the peptide has a length of less than 30 residues.
56. The method of claim 1 , wherein the amino acid segment comprises the amino acid sequence of SEQ ID NO:1 having four or more conservative amino acid substitutions, wherein the peptide has a length of less than 100 residues.
57. The method of claim 1 , wherein the amino acid segment comprises the amino acid sequence of SEQ ID NO:2 having two or more conservative amino acid substitutions, wherein the peptide has a length of less than 90 residues.
58. The method of claim 1 , wherein the moiety is not a polypeptide.