Matrix metalloproteinase cleavable protein polymers for cancer gene therapy
A delivery system that includes a recombinantly synthesized protein polymer with protease cleavage sites such as matrix metalloproteinase responsive sequences engineered within the protein polymer. The system may be used to treat cancer, wounds, or pathological conditions in other tissues that express excess protease relative to healthy tissue.
1. A protein polymer, wherein the protein polymer has the structure: [GAGS(GAGAGS) 2 (GVGVP) 3 GVGGPQGIFGQPGKGVP(GVGVP) 11 (GAGAGS) 5 GA] 6 (SEQ ID NO: 16), and wherein the protein polymer is produced using recombinant methods.
2. A drug delivery system comprising: a. the protein polymer of claim 1 ; and b. a polynucleotide that encodes an enzyme that converts a prodrug to a therapeutically active compound.
3. A drug delivery system according to claim 2 , which comprises a prodrug.
4. A drug delivery system according to claim 2 , wherein the prodrug is provided in a solution comprising the protein polymer and the polynucleotide.
5. A drug delivery system according to claim 3 wherein the prodrug is provided separately from the protein polymer and the polynucleotide.
6. A drug delivery system according to claim 2 , wherein the polynucleotide comprises an adenovirus.
7. A drug delivery system according to claim 2 , wherein the enzyme is thymidine kinase from the Herpes Simplex Virus.
8. A drug delivery system according to claim 2 , wherein the prodrug is ganciclovir.
9. A method of delivering an enzyme that converts a prodrug to a therapeutically active compound to a tissue comprising (1) injecting a solution comprising the protein polymer of claim 1 and a polynucleotide that encodes an enzyme that converts a prodrug to a therapeutically active compound into the tissue; and (2) administering the prodrug to the tissue.