Extended Data Fig. 1: IdeS degrades anti-AAV antibodies and allows successful liver transduction in mice passively immunized with IVIg.
a, IVIg was incubated in vitro with saline (PBS), commercially sourced IdeS (IdeS-C), or lab-made IdeS (IdeS) for 24 hours prior to measurement of anti-AAV8 NAb titers (n = 1 per condition tested in triplicate, one representative out of two independent experiments shown). b, effect of IdeS on AAV8 vector transduction efficiency of HEK293 cells. An AAV8-Luc vector was incubated for 24 hours at 37 °C with PBS (- IdeS) or with increasing amounts of IdeS (+ IdeS). Control, AAV8-Luc not incubated at 37 °C. Relative Light Units (RLU) measured in duplicate at increasing multiplicity of infection (MOI). n = 1 per condition tested in duplicate, one representative out of two independent experiments shown. c, Plasma concentration of IdeS over time in non-human primates (n = 2 animals, duplicate independent measurements of each sample). The inset shows the estimation of the half-life of the enzyme. d, vector genome copy number (VGNC) in passively immunized C57BL/6 mice injected with an AAV8-GLuc vector (n = 6 mice per group, one representative out of two independent experiments shown). e, f, Effect of IdeS on anti-AAV8 IgG e, and NAb titers f, measured 24 hours after treatment in passively immunized HB mice (n = 4 mice per group, data derived from one experiment). g, vector genome copy number (VGNC) in HB mice injected with an AAV8-hFIX vector. All data are shown as mean ± s.d. Statistical analyses were performed by d, one-way ANOVA with Tukey’s multiple comparisons test; e, g, one-way ANOVA with Tukey’s multiple comparisons test; f, one-way ANOVA, non-parametric with Dunn’s multiple comparisons test.
