Fig. 3

Comparing GUIDE-Seq and ITR-Seq in terms of off-target identification. Sample set intersections of identified target sites obtained from in vivo ITR-Seq (coloured) from two doses of AAV8-M1PCSK9 (3 × 10¹³ GC/kg; panel a; and 6 × 10¹² GC/kg; panel b) or one dose of AAV8-M2PCSK9 (6 × 10¹² GC/kg; panels c and d). We obtained target sites on day 17 post-AAV administration. In vitro GUIDE-Seq for M1PCSK9 or M2PCSK9 is shown in gray. Off-target sites identified by ITR-Seq but not by GUIDE-Seq (coloured sections) are indicated as a percent of the total number of off-target sites that were identified by in vivo ITR-Seq. White sections of the Venn diagrams show the proportion of off-target sites that were identified by both ITR-Seq and GUIDE-Seq