Figure 2.

M2PCSK9 Editing In Vivo Expressed by AAV Vectors

Rag1 knockout mice treated with AAV9.hPCSK9 and AAV expressing M2PCSK9 were euthanized at either 4 or 9 weeks post-AAV9.hPCSK9. We then isolated liver DNA from the euthanized mice. (A) Indel% in the target region present in AAV9.hPCSK9. (B) Indel% at 9 weeks post-AAV in the target region. (C) Number of M2PCSK9 off-target loci identified by ITR-seq. (D) Indel% in selected top-ranking off-targets at 9 weeks post-AAV. We have indicated the genomic location for each off target. NT, no target sequences were presented in that vector group. Data is shown as mean ± SEM (n = 5). An asterisk (∗) indicates groups that are statistically different from the AAV8.M2PCSK9 group (p < 0.05, Wilcoxon rank-sum test).