Engineered FGF compositions and methods of use thereof
The present invention relates to the development of stable mutants of FGF-1 and FGF-2. In particular, it relates to novel engineered FGF-1 and FGF-2 polypeptides as well as polynucleotides, DNA constructs, and vectors encoding such polypeptides. In another aspect, pharmaceutical compositions and hydrogels including the disclosed polypeptides, polynucleotides, DNA constructs, and vectors are provided. In a still further aspect, methods of treating conditions using the compositions disclosed herein are provided.
1. A FGF polypeptide comprising a polypeptide selected from the group consisting of SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO: 10, SEQ ID NO: 12, and a polypeptide having 80% sequence identity to SEQ ID NOs: 4, 6, 10 or 12 and comprising amino acid residue of 122 of SEQ ID NO: 4 or SEQ ID NO: 6 or amino acid residue 138 of SEQ ID NO: 10 or SEQ ID NO: 12.
2. The FGF polypeptide of claim 1 , wherein the FGF polypeptide comprises SEQ ID NO: 4 or a polypeptide having 80% sequence identity to SEQ ID NO: 4 and comprising amino acid residue of 122 of SEQ ID NO: 4.
3. The FGF polypeptide of claim 2 , wherein the FGF polypeptide comprises SEQ ID NO: 4.
4. A fusion protein comprising the FGF polypeptide of claim 1 and a membrane permeable peptide.
5. A pharmaceutical composition comprising the FGF polypeptide of claim 1 and a pharmaceutical carrier.
6. A hydrogel comprising the FGF polypeptide of claim 1 .
7. A method of treating a wound comprising administering the FGF polypeptide of claim 1 to a subject in an amount effective to heal the wound.
8. The method of claim 7 , wherein the subject is a human.
9. The FGF polypeptide of claim 1 , wherein the FGF polypeptide comprises SEQ ID NO: 6 or a polypeptide having 80% sequence identity to SEQ ID NO: 6 and comprising amino acid residue of 122 of SEQ ID NO: 6.
10. The FGF polypeptide of claim 9 , wherein the FGF polypeptide comprises SEQ ID NO: 6.
11. A pharmaceutical composition comprising the FGF polypeptide of claim 9 and a pharmaceutical carrier.
12. A hydrogel comprising the FGF polypeptide of claim 9 .
13. The FGF polypeptide of claim 1 , wherein the FGF polypeptide comprises SEQ ID NO: 10 or a polypeptide having 80% sequence identity to SEQ ID NO: 10 and comprising amino acid residue of 138 of SEQ ID NO: 10.
14. The FGF polypeptide of claim 13 , wherein the FGF polypeptide comprises SEQ ID NO: 10.
15. A pharmaceutical composition comprising the FGF polypeptide of claim 13 and a pharmaceutical carrier.
16. A hydrogel comprising the FGF polypeptide of claim 13 .
17. The FGF polypeptide of claim 1 , wherein the FGF polypeptide comprises SEQ ID NO: 12 or a polypeptide having 80% sequence identity to SEQ ID NO: 12 and comprising amino acid residue of 138 of SEQ ID NO: 12.
18. The FGF polypeptide of claim 17 , wherein the FGF polypeptide comprises SEQ ID NO: 12.
19. A pharmaceutical composition comprising the FGF polypeptide of claim 17 and a pharmaceutical carrier.
20. A hydrogel comprising the FGF polypeptide of claim 17 .