Fig. 5: In vivo prime editing at Dnmt1 locus and correction of Pah^enu2 mice using pegRNA-AAV and PE7 mRNA–LNP.

a, Editing rates (top) and indel rates (bottom) at the Dnmt1 locus in mice pretreated with scAAV2/9 expressing the pegRNA tevopreQ1-Dnmt1 at a dose of 2.5 × 10¹³ vg kg⁻¹, which were subsequently injected once with 2 mg kg⁻¹ LNP containing PEmax or PE7 mRNA (n = 4). b, Pah^enu2 correction rates (top) and indel rates (bottom) of mice pretreated with scAAV2/9 expressing the pegRNA tevopreQ1-mPKU-SM4 at a dose of 2.5 × 10¹³ vg kg⁻¹, which were subsequently injected three times with 2 mg kg⁻¹ LNP containing PEmax or PE7 mRNA (n = 7). NGS was performed on isolated hepatocytes, whole liver and tail lysates. c, Phe levels at the experimental end point of homozygous B6 Pah^enu2 mice (n = 7) from b. Dotted lines indicate recommended therapeutic thresholds for Phe levels in adults (600 μmol l⁻¹) or in children/during pregnancy (360 μmol l⁻¹)^29,57. Values represent mean ± s.d. of independent biological replicates.