RPGR gene therapy for retinitis pigmentosa
Methods for treating a human subject who has X-linked Retinitis Pigmentosa (XLRP) or another clinically-defined ophthalmological condition due to a loss-of-function mutation in the gene encoding the retinitis pigmentosa GTPase regulator (RPGR) protein, the method comprising administering to the subject a nucleic acid comprising an adeno-associated viral vector comprising an abbreviated human RPGR cDNA.
1. A method of treating a human subject who has X-linked Retinitis Pigmentosa (XLRP) or another ophthalmological condition due to a loss-of-function mutation in the gene encoding the retinitis pigmentosa GTPase regulator (RPGR) protein, the method comprising administering to an eye of the subject a nucleic acid encoding an abbreviated human RPGR protein, wherein the abbreviated human RPGR protein comprises SEQ ID NO:2.
2. A method of treating a human subject who has X-linked Retinitis Pigmentosa (XLRP) or another ophthalmological condition due to a loss-of-function mutation in the gene encoding the retinitis pigmentosa GTPase regulator (RPGR) protein, the method comprising administering to an eye of the subject a viral vector comprising a nucleic acid encoding an abbreviated human RPGR protein, wherein the abbreviated human RPGR protein comprises SEQ ID NO:2.
3. The method of claim 2 , wherein the nucleic acid is under the control of a human rhodopsin kinase (hRK) promoter.
4. The method of claim 3 , wherein the hRK promoter comprises SEQ ID NO:5.
5. The method of claim 2 , wherein the nucleic acid comprises SEQ ID NO:1.
6. The method of claim 2 , comprising administering the nucleic acid in a dose of about 2×10 10 vg/mL, a dose of about 2×10 11 vg/mL, or a dose of about 2×10 12 vg/mL.
7. The method of claim 2 , wherein the nucleic acid is administered into the subretinal space.
8. The method or use of claim 7 , wherein a micro injection cannula is inserted into the subretinal space, temporal to the optic nerve and just above the major arcade vessels, so that fluid flow can be directed towards the macula.
9. A nucleic acid encoding an abbreviated human RPGR protein, wherein the nucleic acid encodes a protein comprising SEQ ID NO:2.
10. The nucleic acid of claim 9 , wherein the nucleic acid is under the control of a human rhodopsin kinase (hRK) promoter.
11. The nucleic acid of claim 10 , wherein the hRK promoter comprises SEQ ID NO:5.
12. The nucleic acid of claim 10 , wherein the hRK promoter consists essentially of SEQ ID NO:5.
13. A viral vector comprising the nucleic acid of claim 9 .
14. The viral vector of claim 13 , wherein the vector is an adeno-associated viral vector.
15. The viral vector of claim 14 , wherein the adeno-associated viral vector is AAV-2 or AAV-8.
16. An isolated host cell comprising the viral vector of claim 13 .
17. The isolated host cell of claim 16 , wherein the cell expresses the abbreviated human RPGR protein.
18. The method of claim 2 , wherein the viral vector is an adeno-associated viral vector.
19. The method of claim 18 , wherein the adeno-associated viral vector is AAV-2 or AAV-8.
20. The method of claim 1 , wherein the abbreviated human RPGR protein consists of SEQ ID NO:2.
21. The method of claim 2 , wherein the abbreviated human RPGR protein consists of SEQ ID NO:2.
22. The viral vector of claim 14 , wherein the adeno-associated viral vector is AAV2/8.
23. The method of claim 18 , wherein the adeno-associated viral vector is AAV2/8.