CRISPR/Cas9 genome editing is used to alter embryonic stem (ES) cells from Krastm4Tyj mutant mice. The original KrasLSL-G12D mice have a G12D point mutation in exon 2 of the gene and a loxP site flanked STOP element in intron 1. Guide RNAs targeting the KrasG12D site, an ssODN template and the Cas9 nuclease are used to introduce a p.G12C mutation (c.34_36delGGTinsTGC), commonly seen in non-small cell lung cancer. (J:299292)