Fig. 4: AAV-NoSTOP(UGA) restores IDUA activity in IduaKI/KI mice.
From: An engineered UGA suppressor tRNA gene for disease-agnostic AAV delivery
a, Workflow of in vivo assessment of the therapeutic efficacy of rAAV9.2×CuO-hNFS-R8(VG4) or MyoAAV.2×CuO-hNFS-R8(VG4) in IduaKI/KI mice. b, Bar graph showing the IDUA enzymatic activities in the indicated tissues collected from untreated WT mice, untreated IduaKI/KI mice or IduaKI/KI mice treated with rAAV9.2×CuO-hNFS-R8(VG4) and killed at 4 weeks after treatment. Data are normalized to the WT levels as 100%. c, Bar graph showing the IDUA enzymatic activities in the indicated tissues collected from untreated WT mice, untreated IduaKI/KI mice or IduaKI/KI mice treated with MyoAAV.2×CuO-hNFS-R8(VG4) and killed at 4 weeks after treatment. Data are normalized to the WT levels as 100%. d, Bar graph showing the ratios of mouse Idua mRNA to Tbp mRNA (mIdua/mTbp) in the indicated tissues collected from untreated WT mice, untreated IduaKI/KI mice or IduaKI/KI mice treated with MyoAAV.2×CuO-hNFS-R8(VG4). In b–d, each dot represents an individual animal (n = 5 or 6). e, Bar graph showing the vector genome (vg) abundance across various tissues collected from IduaKI/KI mice treated with either rAAV9.2×CuO-hNFS-R8(VG4) (rAAV9) or MyoAAV.2×CuO-hNFS-R8(VG4) (MyoAAV). Each dot represents an individual animal (n = 3 or 4). In b–e, data are presented as the mean and s.d. Statistical analysis was performed using a two-sided unpaired t-test in b,c or one-way ANOVA followed by Dunnett’s multiple-comparison test in d,e. The schematic in a was created with BioRender.com.
