KRAS and cancer: By modifying these pan-KRAS siRNAs with a high proportion of 2′-O-methyl modifications (Hi2OMe), which confers improvements in metabolic stability within the endosomal compartment (55), we found that the KRAS siRNAs (Kseq2 and Kseq3) retained potent RNAi activity in several cancer cell lines (Supplemental Figure 2, D and E).