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 comprising a viral vector comprising an abbreviated human RPGR cDNA, wherein the abbreviated human RPGR cDNA encodes a protein comprising SEQ ID NO:2.
2. The method of claim 1 , wherein the RPGR cDNA is under the control of a human rhodopsin kinase (hRK) promoter.
3. The method of claim 2 , wherein the hRK promoter comprises of SEQ ID NO:5.
4. The method of claim 1 , wherein the RPGR cDNA comprises SEQ ID NO:1.
5. The method of claim 1 , comprising administering the nucleic acid in a low dose of about 2×10 10 vg/mL, a middle dose of about 2×10 11 vg/mL, or a high dose of about 2×10 12 vg/mL.
6. The method of claim 1 , wherein the nucleic acid is administered into the subretinal space.
7. The method or use of claim 6 , 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.
8. A nucleic acid encoding an abbreviated human RPGR, wherein the abbreviated human RPGR cDNA encodes a protein comprising SEQ ID NO:2.
9. The nucleic acid of claim 8 , wherein the RPGR cDNA is under the control of a human rhodopsin kinase (hRK) promoter.
10. The nucleic acid of claim 9 , wherein the hRK promoter comprises SEQ ID NO:5.
11. The nucleic acid of claim 9 , wherein the hRK promoter consists essentially of SEQ ID NO:5.
12. A viral vector comprising the nucleic acid of claim 8 .
13. The viral vector of claim 12 , which is an adeno-associated viral vector.
14. The viral vector of claim 13 , wherein the adeno-associated viral vector is AAV-2, serotype-8 (AAV2/8) or AAV-8.
15. An isolated host cell comprising the viral vector of claim 12 .
16. The isolated host cell of claim 15 , wherein the cell expresses an abbreviated human RPGR protein.
17. The method of claim 1 , wherein the viral vector is an adeno-associated viral vector.
18. The method of claim 17 , wherein the adeno-associated viral vector is AAV-2, serotype-8 (AAV2/8) or AAV-8.
19. 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, wherein the abbreviated human RPGR cDNA encodes a protein comprising SEQ ID NO:2.