Fig. 4: In vivo correction of Pahenu2 mice using pegRNA-AAV and PEmax mRNA–LNP.
From: Treatment of a metabolic liver disease in mice with a transient prime editing approach
a, Schematic illustration of the experimental set-up. b, Pahenu2 correction rates (left) and indel rates (right) in untreated tail tissue (n = 5) or mice treated with scAAV2/9 expressing pegRNA tevopreQ1-mPKU-SM and PE2 or PEmax mRNA–LNP (n = 12). Values represent mean ± s.d. of independent biological replicates and for the indels were analysed using unpaired two-sided Student’s t-tests. c, Phe levels at the experimental end point of untreated homozygous B6 Pahenu2 mice (UT −/−; n = 8) and homozygous B6 Pahenu2 mice treated with scAAVs expressing the pegRNAs tevopreQ1-mPKU-SM and PE2 or PEmax mRNA–LNP (n = 12). Dotted lines indicate recommended therapeutic thresholds for Phe levels in adults (600 μmol l−1) or children/during pregnancy (360 μmol l−1)29,57. Values represent mean ± s.d. of independent biological replicates and were analysed using an ordinary one-way analysis of variance using a Dunnett’s multiple comparisons test. d, Correlation between editing rates in hepatocytes and Phe levels in PEmax (dark magenta) and PE2 (light magenta) treated mice at the experimental end points. R2, coefficient of determination. e, Enzyme activity of PAH in liver tissue lysates from untreated homozygous B6 Pahenu2 mice (n = 2) and homozygous B6 Pahenu2 mice treated with scAAV (pegRNA) and PEmax LNP–mRNA (n = 3). Values are depicted as relative values to PAH activity in wild-type mice. Values represent mean ± s.d. of independent biological replicates.
