COMPOSITIONS AND METHODS FOR OSTEOGENIC GENE THERAPY

摘要

The present disclosure provides compositions and methods for increasing bone growth and/or enhancing wound healing, for example, fracture repair. The disclosure provides recombinant nucleic acids useful for promoting bone growth. For example, the disclosure provides recombinant nucleic acids that encode a fibroblast growth factor-2 (FGF-2) analog. The disclosure also provides vectors and cells incorporating these nucleic acids, as well as FGF-2 analogs encode by them. The disclosure also provides a mouse system of bone marrow transplantation and methods for producing as well as methods for using the system. Methods for inducing division and/or inducing differentiation of a hematopoietic stem cell are also provided, as are methods for enhancing bone growth and/or wound repair (for example, fracture repair).

主权项

1. A recombinant nucleic acid encoding a modified fibroblast growth factor-2 (FGF-2) analog, wherein the nucleic acid comprises in a 5′ to 3′ direction:
a polynucleotide sequence that encodes a BMP2/4 hybrid secretion signal sequence; and a polynucleotide sequence that encodes a mature human FGF-2 polypeptide, wherein the mature human FGF-2 polypeptide comprises at least one of: a mutation that results in the substitution of a glycosylatable amino acid for a cysteine in amino acid position 70 (C2) of FGF-2, and a mutation that results in the substitution of a glycosylatable amino acid for a cysteine in amino acid position 88 (C3) of FGF-2.