Extended Data Figure 10. rAAV.2xsup-tRNA^Tyr treatment efficacy correlates with gene delivery efficiency.

a, IDUA activity in the tibialis anterior (TA) muscle lysates derived from KI/KI mice ± rAAV9.2xsup-tRNA^Tyr treatment via either intravenous (IV) injection of 2x10¹² GC (left panel; n=4 per group) or from KI/KI mice ± rAAV9.2xsup-tRNA^Tyr treatment via intramuscular (IM) injection of 3x10¹¹ GC to the TA muscle (right panel; n=4 or 6 per group). Tissues were harvested at 10 weeks (blue), 4 weeks (yellow), or 12 weeks (orange) post treatment. The right y-axis denotes absolute IDUA specific activity, and the left y-axis denotes relative activity normalized to untreated heterozygous mice as 50% of WT (+/+) level. b, Quantification of AAV vector genome copy numbers in the TA muscle of the mice described in a. c, IDUA enzymatic activity in the TA muscle lysates derived from KI/KI mice ± rAAVMYO.2xsup-tRNA^Tyr treatment via IV injection at 2x10¹² GC (n=4 or 3 per group), and euthanized at 4 weeks post treatment. d, IDUA activity in the brain lysates derived from KI/KI mice ± rAAV.2xsup-tRNA^Tyr treatment via intravenous (IV) injection. Mice were treated with either rAAV9 (left panel; n=4) at 2x10¹² GC or rAAV.PHPeB (right panel; n=5 per group) at 1x10¹¹ GC (yellow) or 2x10¹¹ GC (orange). e, Quantification of AAV vector genome copy numbers in the brain of the mice described in d. f, IDUA activity in the hippocampus lysates derived from KI/KI mice ± rAAV9.2xsup-tRNA^Tyr treatment via intrahippocampal injection of 2.2x10¹⁰ GC (n=4 or 3 per group). Mice were euthanized at 4 weeks post treatment. Data are mean ± s.d. of individual animals (circles). Statistical analysis was performed by one-way Brown-Forsythe and Welch ANOVA followed by two-sided Dunnett T3’s multiple comparisons test (a, c, d, f), or ANOVA followed by two-sided Dunnett’s multiple comparison test (b, e). *p < 0.05, **p < 0.01, ***p < 0.001, ns: not significant.