Kirsten rat sarcoma viral oncogene homolog G12C messenger RNA (KRAS G12C mRNA) (KRAS G12C mRNA)

KRAS G12C mRNA is the messenger RNA transcript that encodes the G12C mutant version of the Kirsten rat sarcoma viral oncogene homolog (KRAS) protein. This transcript contains a specific G-to-T transversion at codon 12, which leads to the production of a mutant GTPase that remains in a constitutively active state, driving oncogenic signaling pathways such as MAPK/ERK and PI3K/AKT (UniProt P01116; PubMed 31663529). While small molecule inhibitors like sotorasib target the protein product, the mRNA itself is a therapeutic target for nucleic acid-based therapies including antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs). These modalities, such as the pan-KRAS ASO AZD4785 or the siRNA LY3537031, aim to reduce the levels of the oncogenic transcript, thereby preventing the synthesis of the KRAS protein and inhibiting tumor growth (PubMed 30530703; NCT04956640). Additionally, synthetic KRAS G12C mRNA is used in cancer vaccines, such as mRNA-5671, to stimulate the immune system to recognize and attack cells expressing the mutant neoantigen (NCT03948191). Targeting the mRNA offers a potential advantage in overcoming resistance to protein-targeted therapies by depleting the source of the oncogenic driver. Overall, KRAS G12C mRNA represents a critical node for precision oncology interventions aimed at the transcriptomic level.

Other names

KRAS G12C transcriptKirsten rat sarcoma 2 viral oncogene homolog G12C mRNAc-K-ras G12C mRNAKRAS*G12C mRNA

Antisense-mediated degradation (RNase H-dependent), RNA interference (RNAi) via the RNA-induced silencing complex (RISC), and mRNA-based vaccination for antigen presentation.