Fig. 4: Genotyping results for the therapeutic effects of sTALED-V28R-AAV for mitochondrial gene therapy in MT-ND4 mutant mouse embryonic fibroblast (MEF) cell lines.
From: In vivo mitochondrial base editing restores genotype and visual function in a mouse model of LHON
a Illustration of selected sTALED-V28R-AAV for MT-ND4 mutant mice mitochondrial gene therapy. TALE sequence shown in navy box and desired locus shown in red (m.G11185A), and undesired edits in MT-ND4 mutant MEF cell line were shown in blue (S339N and T341I). b A heatmap showing base recovery in MT-ND4 mutant MEF cell line #6 after treating sTALED-V28R-AAV via infection. The on-target (m.G11185A) locus is represented with an arrow. Data were shown as means from n = 3 biologically independent samples. c ATP concentrations in WT, MT-ND4 mutant #MEF 6, and MT-ND4 mutant #MEF 6 sTALED-V28R AAV-treated cell lines. The exact p-values were 0.04 on MT-ND4 mutant MEF #6 compared with its sTALED-V28R AAV-treated counterpart, 0.0002 on WT compared with MT-ND4 mutant #MEF 6, and 0.0005 on WT compared with sTALED-V28R AAV-treated MT-ND4 mutant #MEF 6. Error bars indicate standard error of the mean (s.e.m.) for independent samples (n = 3). (*p < 0.05, ***p < 0.001 using Student’s two-tailed t-test). d Oxygen consumption rates of WT, MT-ND4 mutant #6 and MT-ND4 mutant #6 sTALED-V28R AAV- treated MEF cell lines. The error bars indicate the s.e.m. for replicates (n = 4).
