Composition and methods for promoting wound healing and tissue regeneration
View Patent ↗Provided herein are compositions and methods for use in promoting wound healing and tissue regeneration following tissue injury in a subject.
1. A composition comprising at least one polypeptide consisting of the carboxy-terminal most 4 to 30 contiguous amino acids of an alpha connexin protein or conservative variant thereof, wherein said at least one alpha connexin polypeptide is linked at its amino terminus to a cellular internalization transporter.
2. The composition of claim 1 , wherein the cellular internalization transporter is an antennapedia sequence.
3. The composition of claim 2 , wherein the antennapedia sequence is penetratin or Antp-3A.
4. The composition of claim 2 , wherein the antennapedia sequence is SEQ ID NO: 7.
5. The composition of claim 1 , wherein the alpha connexin protein is Connexin 37, Connexin 40, Connexin 43, or Connexin 45.
6. The composition of claim 1 , wherein the at least one polypeptide consists of the carboxy-terminal most 5 to 19 contiguous amino acids of an alpha connexin protein.
7. The composition of claim 1 , wherein the alpha connexin polypeptide consists of the carboxy-terminal most 9 contiguous amino acids of an alpha connexin protein.
8. The composition of claim 1 , wherein the alpha connexin polypeptide has a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 43.
9. The composition of claim 1 , wherein the alpha connexin polypeptide consists of the carboxy-terminal most 8 contiguous amino acids of of an alpha connexin protein.
10. The composition of claim 1 , wherein the alpha connexin polypeptide consists of the carboxy-terminal most 5 contiguous amino acids of an alpha connexin protein.
11. A composition formulated for topical administration comprising a polypeptide consisting of a contiguous sequence of amino acids from the carboxyl terminus of an alpha connexin protein or a conservative variant thereof, wherein said carboxyl terminus includes the sequence up to a transmembrane domain.
12. The composition of claim 11 , wherein the alpha connexin polypeptide consists of between 4 and 30 contiguous carboxy-terminal most amino acids of an alpha connexin protein.
13. The composition of claim 11 , wherein the alpha connexin protein is Connexin 37, Connexin 40, Connexin 43, or Connexin 45.
14. The composition of claim 11 , wherein the alpha connexin polypeptide has a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 43.
15. The composition of claim 14 , wherein the alpha connexin polypeptide is linked at its amino terminus to a cellular internalization transporter.
16. The composition of claim 15 , wherein the cellular internalization transporter is an antennapedia sequence.
17. The composition of claim 16 , wherein the antennapedia sequence is penetratin or Antp-3A.
18. The composition of claim 16 , wherein the antennapedia sequence is SEQ ID NO: 7.
19. The composition of claim 15 , wherein the alpha connexin polypeptide and the cellular internalization transporter together contain the sequence of SEQ ID NO: 9.
20. The composition of claim 14 , wherein the alpha connexin polypeptide has 2 to 5 conservative substitutions as compared to a polypeptide having the sequence of SEQ ID NO: 2.
21. The composition of claim 11 , wherein said formulation for topical administration is an ointment, lotion, spray, cream, or gel.
22. The composition of claim 21 , wherein said gel is a pluronic gel.
23. The composition of claim 21 , wherein said formulation is a poloxamer.
24. The composition of claim 11 further comprising a collagen polymer.
25. The composition of claim 11 further comprising an antibiotic, steroid, analgesic, anti-inflammatory agent, anti-histaminic agent, chemotherapy agent, or other therapeutic peptide, or combination thereof.
26. The composition of claim 11 , wherein said composition comprises between 0.01% w/v or v/v and 2-5% w/v or v/v alpha connexin peptide.
27. The composition of claim 11 , wherein said composition comprises between 10 and 200 μM alpha connexin peptide.
28. A composition comprising a wound-treating material coated with a polypeptide consisting of a contiguous sequence of amino acids from the carboxyl terminus of an alpha connexin protein, wherein said carboxyl terminus includes the sequence up to a transmembrane domain.
29. The wound-treating material of claim 28 , wherein the polypeptide consists of the carboxy terminal most 4 to 30 contiguous amino acids of the alpha connexin protein.
30. The wound-treating material of claim 28 , wherein the material is selected from the group consisting of a bandage, steri-strip, suture, staple, and graft.
31. The wound-treating material of claim 28 , wherein the material is a medical implant.
32. The wound-treating material of claim 28 , wherein the material is a bio-engineered material.
33. The wound-treating material of claim 28 , wherein the material is a tissue engineered scaffold.
34. A method of promoting healing following tissue injury in a subject, comprising administering to the subject a composition of claim 1 , claim 11 or claim 28 .