Extended Data Fig. 4: Designing mutant-selective antisense oligos.
From: Silent mutations reveal therapeutic vulnerability in RAS Q61 cancers
a, Structures of DNA, antisense oligo nucleotides with phosphorothioate (PS) + 2’-O-Methoxyethyl (2’MOE) modifications, and morpholino. In PS+2’MOE, a non-bridging oxygen is replaced by a sulfur atom in the phosphate backbone, and 2′ position of the sugar moiety is modified. In morpholino, the sugar moiety is replaced with methylenemorpholine rings, and the anionic phosphates are replaced with non-ionic phosphorodiamidate linkages. b, Schema depicting the design of the KRAS GQ60GK c.180_181delinsCA, NRAS Q61K, and HRAS Q61L selective antisense oligo. The motifs for binding exonic splicing enhancers simulated using the Human Splicing Finder (top) and ESE finder (bottom) are shown. Matrices for SR proteins including SRSF1 (SF2/ASF and IgM-BRCA1), SRSF2 (SC35), SRSF5 (SRp40), and SRSF6 (SRp55) are shown.
