Figure 1.

Restoration of functional SGSH in MPS IIIA mice following a single systemic scAAVrh74-hSGSH gene delivery. MPS IIIA mice (4–6 weeks old) were treated with an intravenous injection of scAAVrh74-U1a-hSGSH vector (5 × 10¹² vg/kg). At 7 months postinjection, tissues were assayed by (a) SGSH activity assay and immunofluorescence for (b, c) hSGSH and (c, d) GFAP. SGSH activity is expressed as units/mg protein, and 1 unit = mmol of 4MU released/17 hour. +/+: wt; −/−: nontreated MPS IIIA mice; AAV: scAAVrh74-treated MPS IIIA mice. ^#P ≥ 0.05 versus wt; *P ≤ 0.05 versus wt; Liv: liver, Hrt: heart; Int: small intestine; M: muscularis externa. Eye: retina. Red fluorescence: hSGSH-positive cells/signals; green fluorescence: GFAP-positive cells/signals; blue fluorescence: DAPI-stained nuclei. *Red signals in nontreated liver and heat tissues are autofluorescence. Yellow arrows: hSGSH-positive cells and signals; blue arrows: neurons of myenteric plexus; red arrowheads: GFAP-positive staining surrounding myenteric neurons; green arrows: GFAP-positive Müller cells; red arrows: inner nuclear layer; white arrows: outer nuclear layer; yellow arrowheads: pigment layer. Scale bar = 50 μm. AAV, adeno-associated virus; DAPI, 4′,6-diamidino-2-phenylindole; GFAP, glial fibrillary acidic protein; MPS, mucopolysaccharidosis; SGSH, N-sulfoglucosamine sulfohydrolase; vg, vector genome; wt, wild-type.