Fig. 6
From: Enhancing prime editor flexibility with coiled-coil heterodimers
In vivo prime editing to Pcsk9 and its effect on plasma cholesterol levels. a-b. Amplicon sequencing results showing prime editing efficiencies of sPE-P3P4, sPE-N5N6, sPE-ctrl, and PE3 at Pcsk9 in MEFs. c-d. Schematics of dual-AAV sPE-P3P4 (c) and dual-AAV sPE-ctrl (d) architecture. e Schematic of in vivo prime editing. The dual-AAV sPE-P3P4 (n = 3) or dual-AAV sPE-ctrl (n = 3) was delivered to 2-week-old mice via intraperitoneal injection. f Sanger-sequencing chromatograms of sPE-P3P4 and sPE-ctrl harboring the desired insertion at Pcsk9 (+ 2 TAG insertion) locus in mouse livers. The purple arrow denotes the desired insertion. The Pcsk9-specific sgRNA is indicated in red and the PAM sequence is indicated in green. g-i Prime editing (g, h) and indel efficiencies (i) in bulk liver of sPE-P3P4 and sPE-ctrl after injection of AAV to 2-week-old mice (sPE-P3P4, n = 3; sPE-ctrl, n = 3; untreated, n = 2) via intraperitoneal injection (5 × 1011 viral genomes each). j Quantification of total plasma cholesterol levels at 4 weeks after injection. k Quantification of total plasma LDL cholesterol levels at 4 weeks after injection. l Plasma ALT was quantified in noninjected mice and AAV-injected mice. m Plasma AST was quantified in noninjected mice and AAV-injected mice. Statistical significance was determined via unpaired t-tests (*P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns indicating not significant)