AAV-IDS vectors for treatment of mucopolysaccharidosis II

1 . A recombinant nucleic acid comprising a sequence encoding human iduronate-2-sulfatase (IDS) that is codon-optimized for expression in human cells, wherein the recombinant nucleic acid comprises a nucleotide sequence at least 99% identical to SEQ ID NO:1.

2 . The recombinant nucleic acid of claim 1 , comprising the nucleotide sequence of SEQ ID NO:1.

3 . A vector comprising the recombinant nucleic acid of claim 1 .

4 . The vector of claim 3 , comprising the sequence of SEQ ID NO:4 or a sequence at least 90% identical thereto.

5 . An adeno-associated virus (AAV) vector genome comprising the recombinant nucleic acid of claim 1 .

6 . The AAV vector genome of claim 5 , wherein the AAV vector genome is a self-complementary AAV vector genome.

7 . The AAV vector genome of claim 5 , wherein the AAV vector genome comprises the sequence of SEQ ID NO:3 or a sequence at least 90% identical thereto.

8 . The AAV vector genome of claim 5 , wherein the recombinant nucleic acid is operably linked to a constitutive promoter.

9 . The AAV vector genome of claim 8 , wherein the constitutive promoter is a cytomegalovirus promoter.

10 . A cell in vitro comprising the AAV vector genome of claim 5 .

11 . A method of producing a recombinant AAV particle comprising an AAV capsid, the method comprising:

providing a cell in vitro with AAV Cap and AAV Rep coding sequences, the AAV vector genome of claim 5 , and helper functions for generating a productive AAV infection; and

allowing assembly of the recombinant AAV particle comprising the AAV capsid and encapsidating the AAV vector genome.

12 . An AAV particle comprising the AAV vector genome of claim 5 .

13 . The AAV particle of claim 12 , wherein the AAV particle is an AAV9 particle.

14 . A pharmaceutical formulation comprising the AAV particle of claim 12 and a pharmaceutically acceptable carrier.

15 . A method of expressing IDS in a cell, comprising contacting the cell with an effective amount of the AAV particle of claim 12 , thereby expressing IDS in the cell.

16 . A method of increasing secretion of IDS from a cell, comprising contacting the cell with an effective amount of the AAV particle of claim 12 , thereby increasing secretion of IDS from the cell relative to the secretion of IDS after contacting the cell with an AAV particle comprising a nucleic acid comprising the wild-type sequence for IDS.

17 . A method of delivering IDS to a subject, comprising administering to the subject an effective amount of the AAV particle of claim 12 , thereby delivering IDS to the subject.

18 . A method of treating or delaying the onset of mucopolysaccharidosis II (MPS II) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the AAV particle of claim 12 , thereby treating or delaying the onset of MPS II in the subject.

19 . The method of claim 18 , wherein the subject is a human subject.

20 . The method of claim 18 , wherein the subject has been diagnosed with MPS II.