FIBROBLAST GROWTH FACTOR MUTANTS HAVING IMPROVED FUNCTIONAL HALF-LIFE AND METHODS OF THEIR USE

摘要

Mutant fibroblast growth factor (FGF) proteins having a polypeptide sequence with a high sequence identity to proteins encoded by members of the Fgf-1 subfamily of genes from a mammalian species, such as human, and with a specific amino acid substitution of an alanine at a position corresponding to amino acid position 66 of human FGF-1 with a cysteine and/or a specific amino acid substitution of a phenylalanine at a position corresponding to amino acid position 132 of human FGF-1 with a tryptophan (based on the 140 amino acid numbering scheme of human FGF-1) are provided. Other amino acid mutations or substitutions may be combined. Polynucleotide sequences encoding the mutant FGF proteins and host cells containing such polynucleotide sequences are provided. Methods of administering a mutant FGF protein to an individual to treat an ischemic condition or disease or a wound or tissue injury are also provided.

主权项

1. A composition comprising a mutant fibroblast growth factor (FGF) protein having a polypeptide sequence that is at least 90% identical to the wild-type human FGF-1 protein having SEQ ID NO: 1, the alanine at an amino acid position of the mutant FGF polypeptide sequence corresponding to amino acid position 66 of SEQ ID NO: 1 being substituted with cysteine, the mutant FGF protein have a greater functional half-life than SEQ ID NO: 1.