Fig. 5: RNA editing RESTART v3 can restore hearing in Otof c.1315 C > T (p.R439*) mice.
a Representative ABR waveforms in response to sound stimuli in the WT mice and Otof c.1315 C > T (p.R439*) mice treated with RNA editing AAVie-RESTART v3 and AAVie-GFP. ABR waveforms are labeled from I-V. The right panel shows ABR wave I. b Analysis of ABR thresholds was performed in the WT mice, the Otof c.1315 C > T (p.R439*) mice treated with AAVie-RESTART v3 and the AAVie-GFP treated mice, respectively. Data are represented as the mean ± SD. Data was analyzed by two-way ANOVA. AAVie-RESTART v3 versus AAVie-GFP: click, P = 8.576×10⁻6; 4 K, P = 8.576×10⁻6; 8 K, P = 0.0115; 16 K, P = 4.600×10⁻5; 24 K, P = 0.0002. (WT: n = 4 biological samples; AAVie-RESTART v3: n = 3 biological samples; AAVie-GFP: n = 3 biological samples). c Analysis of the latencies (c’1) and amplitudes (c’2) of ABR wave I in the Otof c.1315 C > T (p.R439*) mice treated with AAVie-RESTART v3. d Schematic diagram of auditory startle reflex (ASR) assay. e Representative ASR waveforms of the WT mice, the AAVie-RESTART v3 treated Otof c.1315 C > T (p.R439*) mice (included the 8th week and 6th month after the injection), and the AAVie-GFP treated mice, respectively. f The comparison of ASR elicited probability at the frequencies among the AAVie-RESTART v3 treated Otof c.1315 C > T (p.R439*) mice (the 8th week and 6th month after the injection), and the AAVie-GFP treated mice. Data are represented as the mean ± SD. Data was analyzed by two-way ANOVA. AAVie-RESTART v3 injected 8th week versus 6th month: white noise (WN), P = 0.4447; 4 K, P = 0.3733; 8 K, P = 0.2031; 16 K, P = 0.8295. g Analysis of startle responsive amplitude in the AAVie-RESTART v3 treated Otof c.1315 C > T (p.R439*) mice at 8th week and 6th month after the injection, and the AAVie-GFP treated mice, respectively. Data are represented as the mean ± SD. Data was analyzed by two-way ANOVA. AAVie-GFP versus AAVie-RESTART v3 injected 8th week: WN, P = 0.0002; 4 K, P = 0.0010; 8 K, P = 0.0183; 16 K, P = 0.0007. AAVie-GFP versus AAVie-RESTART v3 injected 6th month: WN, P = 0.0002; 4 K, P = 1.7703×10⁻6; 8 K, P = 8.0975×10⁻5; 16 K, P = 0.0038. f, g: AAVie-RESTART v3: 8th week: n = 4 biological samples; 6th month: n = 4 biological samples; AAVie-GFP: n = 3 biological samples). ns: no significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. Source data are provided as a Source Data file.
