Fig. 5: Targeted adenine base editing of gene csgA on the E. coli TN03 genome in the gut of BALB/c mice following packaged λ cosmid treatment using a non-replicative payload.
From: In situ targeted base editing of bacteria in the mouse gut
a, Summary of the experimental set-up. Five days following colonization, mice were treated with packaged cosmids equipped with gpJ A8 and λ-K5 STF chimera encoding an ABE targeting the csgA gene. In one arm we investigated the dose–response and in the other the impact of multiple doses on treatment efficacy. b, Editing efficacy 24 h following a single dose at decreasing concentration (n = 10 independent animals per group, ****P < 0.0001 by one-way ANOVA with Tukey’s multiple-comparisons test). Bars represent mean ± s.d. c, Family-level bacterial composition quantified by metagenomic 16S sequencing before (D4) and after treatment (D12) with 1 × 1010 particles (n = 10 animals); data for all mice and time points are provided in Extended Data Fig. 10. Boxes are drawn from the first to third quartile, with the midline representing the median; whiskers extend to the minimum and maximum in each category, excluding outliers shown as black diamonds. d, Changes in intestinal microbiome composition of individual mice over time, represented as weighted UniFrac distance from the D5 sample. Stool samples of mice treated with 1 × 1010 particles were analysed (n = 9 animals). The plot is drawn as in c. e, Editing efficacy following multiple treatments (P values indicated on the graph; NS, P > 0.05 by one-way ANOVA with Tukey’s multiple-comparisons test; n = 14 animals); treatments are indicated by black arrowheads on the x axis). Points show individual mice and bars represent the group median, with 95% confidence interval when applicable. Panel a created with BioRender.com.
