Figure 2.

Supraphysiological IDS activity levels after gene therapy

Two-month-old Ids^y/− mice were treated with gene therapy using 9 Gy total body irradiation (TBI) and the indicated multiplicity of infection (MOI). Gene therapy was performed in two separate experiments, as indicated. (A) VCN per genome measured in bone marrow by qPCR on PSI and Albumin loci. (B) Chimerism in bone marrow measured by flow cytometry and expressed as percentage of CD45.1⁺/CD45.2⁻ cells. For IDSco and IDS.IGF2co, MOI 1 groups from experiments 1 and 2 were combined in the same graph. (C) IDS enzyme activity in bone marrow. (D) Non-linear regression analysis between vector copy number and IDS enzyme activity in bone marrow. (E) IDS enzyme activity in plasma. (F) Linear regression analysis between vector copy number in bone marrow and IDS enzyme activity in plasma. Regression analysis of (D and F) is shown in Table S1. Data represent means ± SEM and were analyzed by one-way ANOVA followed by Bonferroni’s multiple testing correction. Experiment 1: n = 5 or 6 per group. Experiment 2: IDSco, IDS.IGF2co, GFP, Ids^y/− and WT n = 6; IDS.ApoE2co n = 10; IDS.RAP12x2co n = 7. ∗p ≤ 0.05, ∗∗∗p ≤ 0.001, ∗∗∗∗p ≤ 0.0001. Significant results are indicated by brackets.