Supplementary Figure 3: Exome-guided design of precision MAEGI to activate endogenous mutant genes.

a, Exome sequencing identified genic mutations in E0771 cells, indicated over their positions in the mouse genome. Genes were colored by the presence or absence of SNPs and/or indels. b, Scatter plot showing the number of mutations as SNPs or indels per gene. Genes were filtered by a minimum number of total mutations in E0771 cells compared to wildtype C57BL/6J mammary fat pad. Examples of the most highly mutated genes are Tekt2, Hmmr, Acer2, G3bp1, Rsc1a1, Slu7, Fat2 and Skint3. A total of 1,116 genes were used in custom library design. c, Violin density plot of sgRNA representation in the E0771 exome-guided AAV-p-MAEGI plasmid library (n = 3,839 sgRNAs), showing 100% representation of the library. d, Representative images of mice at experimental end-point from PBS, AAV-Vector, and AAV-p-MAEGI groups in the E0771 syngeneic tumor model. e, Growth curves of E0771 syngeneic tumors in Rag1^–/– mice treated by PBS (n = 6), AAV-Vector (n = 5), or AAV-p-MAEGI (n = 6) by intratumoral administration at indicated times (blue arrows). n = biologically independent mice. Two-way ANOVA: AAV-Vector vs. PBS, p = 0.0653; AAV-p-MAEGI vs. PBS, p = 0.6982; AAV-p-MAEGI vs. AAV-Vector, p = 0.0634. Error bars: All data in this figure are presented as mean ± s.e.m., with individual data points shown. Asterisks: * p < 0.05, ** p < 0.01, *** p < 0.001.