Kirsten rat sarcoma virus oncogene homolog G12D messenger RNA (KRAS G12D mRNA)

KRASG12D mRNA is the messenger RNA transcript encoding the KRAS protein with a glycine-to-aspartate substitution at codon 12. This specific mutation is a predominant driver in several lethal cancers, most notably appearing in approximately 40% of pancreatic ductal adenocarcinomas and significant portions of colorectal and lung cancers [Source: Waters and Der, 2018, Cold Spring Harbor Perspectives in Medicine]. The resulting G12D protein remains in a constitutively active, GTP-bound state, triggering downstream signaling pathways like MAPK and PI3K that promote uncontrolled cell proliferation and survival [Source: Simanshu et al., 2017, Cell]. By targeting the mRNA transcript, therapeutic interventions aim to prevent the translation of this oncogenic protein entirely. Current strategies include RNA interference (RNAi) using siRNAs such as siG12D-LODER to degrade the transcript [Source: Golan et al., 2015, Oncotarget] and mRNA-based vaccines like mRNA-5671 (V941) that use the sequence to prime the immune system against G12D-mutant cells [Source: ClinicalTrials.gov, NCT03948763]. This approach bypasses the historical difficulty of targeting the KRAS protein's smooth surface with traditional small molecules.

Other names

KRAS p.G12D mRNAKRAS*G12D mRNAKirsten rat sarcoma proto-oncogene G12D mRNAKRAS proto-oncogene GTPase G12D mRNA

RNA interference (RNAi) mediated degradation of mRNA and translation of mRNA into neoantigens for immune stimulation.