Silencing of Oncogenic KRAS by Mutant-Selective Small Interfering RNA.

ABSTRACT: Oncogenic mutations in the KRAS gene are well-established drivers of cancer. While the recently developed KRAS^G12C inhibitors offer a targeted KRAS therapy and have shown success in the clinic, KRAS^G12C represents only 11% of all KRAS mutations. Current therapeutic approaches for all other KRAS mutations are both indirect and nonmutant-selective, largely focusing on inhibition of downstream KRAS effectors such as MAP kinases. Inhibition of KRAS downstream signaling results in a system-wide down-modulation of the respective targets, raising concerns about systemic cell toxicity. Here, we describe a custom short interfering RNA oligonucleotide (EFTX-D1) designed to preferentially bind mRNA of the most commonly occurring KRAS missense mutations in codons 12 and 13

SUBMITTER: Papke B 

PROVIDER: S-EPMC8033609 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature