Claims
- 1. A polynucleotide comprising a nucleic acid sequence encoding a lysosomal enzyme, a secreted protein, a nuclear protein, or a cytoplasmic protein operably linked to a nucleic acid sequence encoding a protein transduction domain (PTD).
- 2. The polynucleotide of claim 1, wherein the nucleic acid sequence encodes a lysosomal enzyme.
- 3. The polynucleotide of claim 2, wherein the lysosomal enzyme is a soluble lysosomal enzyme.
- 4. The polynucleotide of claim 3, wherein the soluble lysosomal enzyme is β-glucuronidase, pepstatin insensitive protease or palmitoyl protein thioesterase.
- 5. The polynucleotide of claim 3, wherein the soluble lysosomal enzyme is β-glucuronidase.
- 6. The polynucleotide of claim 1, wherein the nucleic acid sequence encodes a secreted protein.
- 7. The polynucleotide of claim 2, wherein the secreted protein is a growth factor or an anti-neoplastic protein.
- 8. The polynucleotide of claim 7, wherein the growth factor is GDNF, NGF, BDNF, or NT3.
- 9. The polynucleotide of claim 7, wherein the anti-neoplastic protein is an inhibitor of neovascularization, cell migration, or cell proliferation.
- 10. The polynucleotide of claim 1, wherein the polynucleotide is a nuclear protein.
- 11. The polynucleotide of claim 10, wherein the nuclear protein is a transcription factor.
- 12. The polynucleotide of claim 1, wherein the polynucleotide is a cytoplasmic protein.
- 13. The polynucleotide of claim 12, wherein the cytoplasmic protein is a cytotoxic agent.
- 14. The polynucleotide of claim 1, wherein the PTD is Tat PTD.
- 15. The polynucleotide of claim 14, wherein the Tat PTD is Tat47-57.
- 16. An expression vector comprising a nucleic acid sequence encoding a lysosomal enzyme, a naturally secreted protein, a nuclear protein, or a cytoplasmic protein operably linked to a nucleic acid sequence encoding a PTD.
- 17. The vector of claim 16, wherein the nucleic acid sequence encodes a lysosomal enzyme.
- 18. The vector of claim 16, wherein the lysosomal enzyme is a soluble lysosomal enzyme.
- 19. The vector of claim 18, wherein the soluble lysosomal enzyme is β-glucuronidase, pepstatin insensitive protease or palmitoyl protein thioesterase.
- 20. The vector of claim 19, wherein the soluble lysosomal enzyme is β-glucuronidase
- 21. The vector of claim 16, wherein the nucleic acid sequence encodes a secreted protein.
- 22. The vector of claim 21, wherein the secreted protein is a growth factor or an anti-neoplastic protein.
- 23. The vector of claim 22, wherein the growth factor is GDNF, NGF, BDNF, or NT3.
- 24. The vector of claim 22, wherein the anti-neoplastic protein is an inhibitor of neovascularization, cell migration, or cell proliferation.
- 25. The vector of claim 16, wherein the nucleic acid is a nuclear protein.
- 26. The vector of claim 25, wherein the nuclear protein is a transcription factor.
- 27. The vector of claim 16, wherein the nucleic acid is a cytoplasmic protein.
- 28. The vector of claim 27, wherein the cytoplasmic protein is a cytotoxic agent.
- 29. The vector of claim 16, wherein the PTD is Tat PTD.
- 30. The vector of claim 29, wherein the Tat PTD is Tat47-57.
- 31. The vector of claim 16, wherein the vector is an adenoviral vector.
- 32. The vector of claim 16, wherein the vector is an adeno-associated virus vector.
- 33. The vector of claim 16, wherein the vector is a recombinant lentivurs or retrovirus vector.
- 34. A polypeptide comprising a lysosomal enzyme, a naturally secreted protein, a nuclear protein, or a cytoplasmic protein operably linked to a nucleic acid sequence encoding a PTD.
- 35. The polypeptide of claim 34, wherein the polypeptide is a lysosomal enzyme.
- 36. The polypeptide of claim 34, wherein the lysosomal enzyme is a soluble lysosomal enzyme.
- 37. The polypeptide of claim 36, wherein the soluble lysosomal enzyme is β-glucuronidase, pepstatin insensitive protease or palmitoyl protein thioesterase.
- 38. The polypeptide of claim 36, wherein the soluble lysosomal enzyme is β-glucuronidase
- 39. The polypeptide of claim 34, wherein the polypeptide is a secreted protein.
- 40. The polypeptide of claim 39, wherein the secreted protein is a growth factor or an anti-neoplastic protein.
- 41. The polypeptide of claim 40, wherein the growth factor is GDNF, NGF, BDNF, or NT3.
- 42. The polypeptide of claim 40, wherein the anti-neoplastic protein is an inhibitor of neovascularization, cell migration, or cell proliferation.
- 43. The polypeptide of claim 34, wherein the polypeptide is a nuclear protein.
- 44. The polypeptide of claim 43, wherein the nuclear protein is a transcription factor.
- 45. The polypeptide of claim 34, wherein the polypeptide is a cytoplasmic protein.
- 46. The polypeptide of claim 45, wherein the cytoplasmic protein is a cytotoxic agent.
- 47. The polypeptide of claim 34, wherein the PTD is Tat PTD.
- 48. The polypeptide of claim 47, wherein the Tat PTD is Tat47-57.
- 49. A mammalian cell comprising the vector of claim 12.
- 50. The cell of claim 49, wherein the cell is human.
- 51. The cell of claim 49, wherein the cell is from spleen, kidney, lung, heart, liver or brain.
- 52. The cell of claim 49, wherein the cell is a stem or progenitor cell.
- 53. A method of treating a genetic disease or cancer in a mammal comprising administering the polynucleotide of claim 1.
- 54. The method of claim 53, wherein the mammal is human.
- 55. The method of claim 53, wherein the genetic disease is a lysosomal storage disease (LSD).
- 56. The method of claim 55, wherein the LSD is infantile or late infantile ceroid lipofuscinoses, Gaucher, Juvenile Batten, Fabry, MLD, Sanfilippo A, Late Infantile Batten, Hunter, Krabbe, Morquio, Pompe, Niemann-Pick C, Tay-Sachs, Hurler (MPS-I H), Sanfilippo B, Maroteaux-Lamy, Niemann-Pick A, Cystinosis, Hurler-Scheie (MPS-I H/S), Sly Syndrome (MPS VII), Scheie (MPS-I S), Infantile Batten, GM1 Gangliosidosis, Mucolipidosis type II/III, or Sandhoff disease.
- 57. The method of claim 53, wherein the genetic disease is a neurodegenerative disease.
- 58. The method of claim 57, wherein the neurodegenerative disease is Huntington's disease, ALS, hereditary spastic hemiplegia, primary lateral sclerosis, spinal muscular atrophy, Kennedy's disease, Alzheimer's disease, a polyglutamine repeat disease, or focal exposure such as Parkinson's disease.
- 59. A method of treating a genetic disease or cancer in a mammal comprising administering the vector of claim 16.
- 60. A method of treating a genetic disease or cancer in a mammal comprising administering the polypeptide of claim 34.
- 61. A method of treating a genetic disease or cancer in a mammal comprising administering the cell of claim 49.
Government Interests
[0001] Portions of the present invention were made with support of the United States Government via a grant from the National Institutes of Health under grant numbers HD33531 and NS34568. The U.S. Government therefore may have certain rights in the invention.