Intracellular delivery of osteoinductive proteins and peptides
AssigneeWarsaw Orthopedic, In Emory University
InventorsFrances Titus, Jeffrey Marx, Scott Boden, Sangwook Yoon, Susan Drapeau
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Abstract
The invention provides fusion polypeptides comprising protein transduction domains and osteoinductive polypeptides, as well as methods of using such polypeptides to induce osteogenesis and to promote proteoglycan synthesis. The invention also provides osteoinductive peptides which have demonstrated the ability to induce bone formation in vivo.
Claims43
A method of producing a cell-permeable osteoinductive polypeptide comprising introducing into a suitable host cell an expression construct comprising:
- a) a polynucleotide encoding a cell-permeable polypeptide;
- b) a polynucleotide encoding an osteoinductive polypeptide operably linked to the cell-permeable polypeptide and positioned so that the osteoinductive polypeptide is expressed as part of a fusion protein with the cell-permeable polypeptide;
- c) a promoter positioned to direct transcription of the polynucleotides.
A method of inducing bone formation in a mammal comprising administering an effective amount of a fusion polypeptide comprising a protein transduction domain and at least one osteoinductive polypeptide.
A polynucleotide encoding a fusion protein comprising a protein transduction domain and at least one osteoinductive polypeptide.
A method of inducing proteoglycan synthesis in a mammal comprising administering an effective amount of a fusion polypeptide comprising a protein transduction domain and at least one osteoinductive polypeptide.
An isolated fusion polypeptide comprising a membrane-translocating peptide operably linked to an osteoinductive polypeptide.
A method of inducing osteoblast differentiation in a progenitor cell, the method comprising administering to the progenitor cell an effective amount of a fusion polypeptide comprising a protein transduction domain and at least one osteoinductive polypeptide.
An osteoinductive polypeptide chosen from among the group consisting of SEQ ID NO 1, SEQ ID NO 2, SEQ ID NO 3, SEQ ID NO 4, SEQ ID NO 5, SEQ ID NO 6, SEQ ID NO 7, and SEQ ID NO 8, or combinations thereof.
42 An osteoinductive polypeptide which hybridizes under standard conditions to a nucleic acid molecule complementary to the sequence:
- tcctcatccg ggtcttgcat gaactcggtg.
An osteoinductive polypeptide which hybridizes under highly stringent conditions to a nucleic acid molecule complementary to the sequence:
- gcccccgccc gctgacagcg ccccgcaa.
Dependencies are inferred from the claim text.