AAV-IDUA vector for treatment of MPS I-associated blindness
This invention relates to viral vectors for delivery of alpha-L-iduronidase to the cornea of a subject and methods of using the same for treatment and prevention of corneal clouding and blindness in a subject due to mucopolysaccharidosis I.
1. A method of delivering alpha-L-iduronidase (IDUA) to the cornea of a subject, comprising administering to the cornea of the subject an effective amount of an AAV particle comprising a nucleic acid encoding IDUA operably linked to a promoter by intrastromal injection, intravitreal administration, and/or subretinal administration, thereby delivering IDUA to the cornea of the subject.
2. A method of treating mucopolysaccharidosis I (MPS I)—associated corneal clouding in a subject in need thereof, comprising administering to the cornea of the subject a therapeutically effective amount of an AAV particle comprising a nucleic acid encoding IDUA operably linked to a promoter, thereby treating MPS I-associated corneal clouding in the subject.
3. The method of claim 1 , wherein the AAV particle is administered to the cornea by intrastromal injection.
4. The method of claim 1 , wherein the subject is a human subject.
5. The method of claim 1 , wherein the subject has been diagnosed with MPS I.
6. The method of claim 1 , wherein the subject has not developed clouding of the cornea.
7. The method of claim 1 , wherein the subject has developed clouding of the cornea.
8. The method of claim 1 , wherein the IDUA is a human IDUA and the nucleic acid encoding human IDUA comprises a nucleotide sequence that has been codon-optimized for expression in human cells.
9. The method of claim 8 , the nucleic acid comprises the nucleotide sequence of SEQ ID NO: 1.
10. The method of claim 1 , wherein the AAV particle is an AAV2, AAV8, or AAV9 particle.
11. The method of claim 1 , wherein the AAV particle is a chimeric AAV8/AAV9 particle.
12. The method of claim 2 , wherein the AAV particle is administered to the cornea by intrastromal injection.
13. The method of claim 2 , wherein the AAV particle is administered to the cornea topically.
14. The method of claim 2 , wherein the subject is a human subject.
15. The method of claim 2 , wherein the subject has been diagnosed with MPS I.
16. The method of claim 2 , wherein the IDUA is a human IDUA and the nucleic acid encoding human IDUA comprises a nucleotide sequence that has been codon-optimized for expression in human cells.
17. The method of claim 15 , wherein the nucleic acid comprises the nucleotide sequence of SEQ ID NO: 1.
18. The method of claim 2 , wherein the AAV particle is an AAV2, AAV8, or AAV9 particle.
19. The method of claim 2 , wherein the AAV particle is a chimeric AAV8/AAV9 particle.