Fig. 2: In vivo prime editing using RNA–LNP delivery.
From: Treatment of a metabolic liver disease in mice with a transient prime editing approach
a, Expression kinetics of PE mRNA and protein (n = 2 mice). Relative values were normalized to the respective housekeeping gene and the average observed peak expression (6 and 28 h.p.i., respectively). b, In vitro editing rates at the Dnmt1 locus (left) and Pahenu2 locus (right) after electroporation of HEK293T reporter cells with modified pegRNAs. IVT, in vitro transcribed. Values represent mean ± s.d. of three independent biological replicates. c,e, Schematic illustration of the experimental set-ups. Mice were dosed with PEmax mRNA 14 h before pegRNA injection for a total of two injection rounds targeting the Dnmt1 locus and three injections rounds for the Pah locus (c), or PEmax was co-delivered with the respective pegRNA twice for the Dnmt1 locus and three times for the Pah locus (e). d, In vivo editing rates of the Dnmt1 locus in C57BL/6J mice (left; n = 3) and of the Pahenu2 locus in homozygous (−/−) B6 Pahenu2 mice (right; n = 3 with unmodified pegRNA and phosphonoacetate (PACE)-DNA-modified pegRNA, n = 6 with PACE-modified pegRNA). f, In vivo editing rates at the Dnmt1 locus in C57BL/6J mice (left; n = 4 for 1× co-injection and n = 3 for the other combinations) and at the Pahenu2 locus in homozygous (−/−) B6 Pahenu2 mice (right; n = 3). In a, b, d and f, values represent mean ± s.d. of independent biological replicates.
