Figure 1

Generation and characterization of Cre-dependent dCas9-VPR-expressing mice. (A) Scheme of the Cre-dependent dCas9-VPR Rosa26 targeting vector. (B) Outline of the in vivo experiment. Rosa26-LSL-dCas9-VPR mice were iv injected with AAV8 containing LP1-Cre gene (AAV8-Cre) or 6 different gRNAs against Pcsk9 (AAV8-gPcsk9), named gPcsk9-1 to 6, at the amount of 1 × 1011 VG/mouse. 21 days later mice were sacrificed, and tissues were collected for analysis. (C) PCR representation showing LSL cassette recombination in liver tissues isolated from Rosa26-LSL-dCas9-VPR mice transduced with AAV8-Cre or AAV8-gPCSK9 alone. A representative agarose gel electrophoresis image is shown. Lane 1–3 contains amplicons obtained from tissue samples of three different mice treated with AAV8-gPcsk9 and lanes 4–6 from tissue samples of three different mice treated with AAV8-Cre. The expected size of PCR products, marker (M) and NTC (H2O) are indicated. (D) dCas9-VPR RNA expression in tissues dissected from AAV8-Cre or AAV8-gPCSK9 injected Rosa26-LSL-dCas9-VPR mice. dCas9-VPR expression can only be seen in AAV8-Cre treated Rosa26-LSL-dCas9-VPR mice liver samples. Mean values are shown as a relative quantification, with corresponding expression level of AAV-Cre treated control group as a reference (n = 10).