Fig. 5: RIDE treatment rescued the motor deficits in the Huntington’s disease model.
a, Illustration of gRNA pairs designed to delete the polyQ repeats in the first exon of the HTT gene. b, Western blot analysis of the downregulation of HTT expression by RIDE in HeLa cells. RIDE was pseudotyped with hyRV-G or VSV-G. A representative result is shown from two biologically independent replicates. c, Schematic illustration of the behaviour study. Q175 mice were injected with RIDE-hmHTT (680 ng p24/both sides of the striatum), n = 15 mice (9 males and 6 females); or RIDE-scramble (680 ng p24/both sides of the striatum), n = 15 mice (7 males and 8 females). WT C57BL/6J mice were included as healthy control, n = 13 mice (6 males and 7 females). After 10 months, the behaviour tests were performed. d, Body weight changes of Q175 and WT mice 6 months after RIDE injection. Unpaired one-sided nonparametric test analysis. RIDE-hmHTT versus RIDE-scramble male mice, *P = 0.0281; RIDE-hmHTT versus RIDE-scramble female mice, *P = 0.0406. e, Mice were subjected to the cylinder test. WT mice versus RIDE-scramble Q175, *P = 0.0182; RIDE-hmHTT versus RIDE-scramble, *P = 0.0408. f, Clasping test. WT mice versus RIDE-scramble Q175, *P = 0.0157. g–i, Grid walk test. Times (g), WT mice versus RIDE-hmHTT Q175, ***P = 0.0009; WT mice versus RIDE-scramble Q175, ***P < 0.0001; errors (h), WT mice versus RIDE-scramble Q175, ***P = 0.0004; RIDE-hmHTT versus RIDE-scramble, ***P < 0.0001; steps (i), WT mice versus RIDE-scramble Q175, ***P < 0.0001; RIDE-hmHTT versus RIDE-scramble, *P = 0.0152. Data represent the mean ± s.e.m. A one-way ANOVA was applied.
