Fig. 5. Inducible in vivo editing of mouse PCSK9 gene.

a Triple AAVs encoding sABE v3.22. IntN and IntC refer to the N- and C-terminal parts of the gp41-1 intein, respectively. b A-to-G base editing efficiencies at Site 9 A₅ in HEK293T cells transduced with triple AAVs encoding sABE v3.22. n = 3. c Schematic of ABE-mediated mPCSK9 gene knockout. The intron 1 splice donor is emboldened, and the target adenine is highlighted in red. d Dual AAVs encoding sABE v3.22 for in vivo editing. e A-to-G editing efficiencies at mPCSK9 intron 1 splice donor site in the HEK293T stable cell line integrated with a 200-bp mPCSK9 exon 1-intron 1 junction. sABE v3.22 was induced with 200 nM rapamycin. Editing efficiencies were assessed 14 days after the dual-AAV transduction. n = 6. f Schematic outline of the mouse experiment. Vectors in d were administered intravenously via tail vein injection into C57BL/6 J mice. 3 mg/kg rapamycin was dosed via i.p. injection every other day four times. g A-to-G base editing efficiencies at mPCSK9 intron 1 splice donor site in mouse liver tissue. n = 4 animals in each group. Vehicle-Only: Mock-injected with the vehicle. High-throughput sequencing reads consisting of <0.2% of total reads were not considered. Dots represent individual biological replicates, and bars represent mean ± s.d.