a, Single-vector AAV system and experimental timeline. b, Indels at Pcsk9 targets in liver tissue following injection of AAV at 2E11 total genome copies (n=3 animals). Time course of c, serum Pcsk9 and d, total cholesterol in animals (n=3 for all titers and time points, error bars show S.E.M.). e, Manhattan plots of BLESS-identified DSB clusters in N2a cells. Inset indicates indel levels at top DSB scoring loci. f, Indels in liver tissue (n=3 animals, error bars indicate Wilson intervals) at BLESS-identified off-target loci. Heatmap indicates DSB scores.