Fig. 6: In vivo validation of the all-in-one AAV/ dSaCas9- KRAB-MeCP2(TRD) repressor platform using ApoE in mouse hippocampus. | Nature Communications

Fig. 6: In vivo validation of the all-in-one AAV/ dSaCas9- KRAB-MeCP2(TRD) repressor platform using ApoE in mouse hippocampus.

From: The therapeutic implications of all-in-one AAV-delivered epigenome-editing platform in neurodegenerative disorders

Fig. 6

The all-in-one AAV/ dSaCas9- KRAB-MeCP2(TRD) repressor platform and the control vector AAV/dSaCas9 with no repressor were administered by stereotaxic injection into the mouse dorsal hippocampus (DH) and validated using the mouse endogenous Apoe gene (a, b) AAV/gRNA(Apoe)p-dSaCas9-KRAB-MeCP2(TRD) vectors with gRNA1 or gRNA2 were injected into the right DH and the control AAV/dSaCas9 into the left DH. Both AAV/gRNA (Apoe)p-dSaCas9-KRAB-MeCP2(TRD) vectors reduced the mouse endogenous ApoE expression. a Representative images of brain coronal slices at 2× magnification 42 days post-injection, showing ApoE expression and DAPI staining in the DH; 20× magnification of DH region showing ApoE expression. b Signals were quantified using ImageJ. Box plot displays the ratios of the right DH relative to the left DH for mice injected with the repressor vector harboring gRNA1 (n = 8, p = 0.0002) and gRNA2 (n = 8, p = 0.0011). Each open circle represents the quantified signal right/left for a mouse. Values represent mean ± SEM. *p < 0.05 **p < 0.01 ***p < 0.001; Two -tailed Mann–Whitney U-Test. Source data are provided as a Source Data file.

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