Compositions and methods of using chondroitinase ABCI mutants
View Patent ↗One aspect of the present invention relates to mutants of chondroitinase ABCI. Such chondroitinase ABCI mutants exhibit altered chondroitin lyase activity or increased resistance to inactivation from stressors including exposure to UV light or heat. Methods of using chondroitinase ABCI mutant enzymes are also provided.
1. An isolated mutant chondroitinase ABCI enzyme selected from BC9 (SEQ ID NO:4), BC7 (SEQ ID NO:5), RD4 (SEQ ID NO:6), and BE11 (SEQ ID NO:7).
2. The isolated mutant chondroitinase ABCI enzyme of claim 1 , wherein said enzyme comprises BC9 (SEQ ID NO:4).
3. The isolated mutant chondroitinase ABCI enzyme of claim 1 , wherein said enzyme comprises BC7 (SEQ ID NO:5).
4. The isolated mutant chondroitinase ABCI enzyme of claim 1 , wherein said enzyme comprises RD4 (SEQ ID NO:6).
5. The isolated mutant chondroitinase ABCI enzyme of claim 1 , wherein said enzyme comprises BE11 (SEQ ID NO:7).
6. A method of treating a central nervous system injury comprising administering a therapeutically effective amount of an isolated mutant chondroitinase ABCI enzyme selected from BC9 (SEQ ID NO:4), BC7 (SEQ ID NO:5), RD4 (SEQ ID NO:6), and BE11 (SEQ ID NO:7).
7. The method of claim 6 , wherein the isolated mutant chondroitinase ABCI enzyme is administered following a contusion injury to the central nervous system.
8. The method of claim 6 , wherein the isolated mutant chondroitinase ABCI enzyme is administered following a non-contusion injury to the central nervous system.
9. The method of claim 6 , wherein the isolated mutant chondroitinase ABCI enzyme is administered following a spinal cord injury.
10. The method of claim 6 , wherein the isolated mutant chondroitinase ABCI enzyme is administered locally.
11. The method of claim 10 , wherein the local administration is selected from intrathecal and topical administration.
12. The method of claim 6 , wherein said enzyme comprises BC9 (SEQ ID NO:4).
13. The method of claim 6 , wherein said enzyme comprises BC7 (SEQ ID NO:5).
14. The method of claim 6 , wherein said enzyme comprises RD4 (SEQ ID NO:6).
15. The method of claim 6 , wherein said enzyme comprises BE11(SEQ ID NO:7).
16. A method of promoting neuronal outgrowth comprising administering a therapeutically effective amount of an isolated mutant chondroitinase ABCI enzyme selected from BC9 (SEQ ID NO:4), BC7 (SEQ ID NO:5), RD4 (SEQ ID NO:6), and BE11 (SEQ ID NO:7).
17. The method of claim 16 , wherein the isolated mutant chondroitinase ABCI enzyme is administered following a contusion injury to the central nervous system.
18. The method of claim 16 , wherein the isolated mutant chondroitinase ABCI enzyme is administered following a non-contusion injury to the central nervous system.
19. The method of claim 16 , wherein the isolated mutant chondroitinase ABCI enzyme is administered following a spinal cord injury.
20. The method of claim 16 , wherein the isolated mutant chondroitinase ABCI enzyme is administered locally.
21. The method of claim 20 , wherein the local administration is selected from intrathecal and topical administration.
22. The method of claim 16 , wherein said enzyme comprises BC9 (SEQ ID NO:4).
23. The method of claim 16 , wherein said enzyme comprises BC7 (SEQ ID NO:5).
24. The method of claim 16 , wherein said enzyme comprises RD4 (SEQ ID NO:6).
25. The method of claim 16 , wherein said enzyme comprises BE11 (SEQ ID NO:7).