Kirsten rat sarcoma viral oncogene homolog G12V mutant messenger RNA (KRAS G12V mRNA) (KRAS G12V mRNA)

KRAS G12V mutant messenger RNA (mRNA) is the transcript produced from the mutated KRAS gene, where a point mutation results in a valine instead of glycine at position 12 of the protein (Prior et al., 2020, Cancer Research). This mRNA is a critical therapeutic target because it encodes a constitutively active form of the KRAS GTPase, which promotes oncogenic signaling through the MAPK and PI3K pathways (Simanshu et al., 2017, Cell). The presence of this mutant transcript leads to aggressive tumor growth and is particularly prevalent in pancreatic, colorectal, and lung cancers. Therapeutic strategies targeting this mRNA include RNA interference (RNAi) using siRNAs and antisense oligonucleotides (ASOs) that bind to the mutant sequence to induce degradation (Khvorova & Watts, 2017, Nature Biotechnology). Furthermore, mRNA-based vaccines utilize synthetic versions of this mutant sequence to induce a T-cell mediated immune response against the G12V neoantigen (Moderna, 2024, Pipeline). By targeting the mRNA, researchers aim to silence the expression of the KRAS protein or leverage its unique sequence for immunotherapy, bypassing the historical challenges of direct protein inhibition. However, ensuring high specificity to avoid silencing the essential wild-type KRAS mRNA remains a significant pharmacological challenge (Golan et al., 2015, Oncotarget).

Other names

KRAS*G12V mRNAKRAS G12V transcriptKirsten rat sarcoma 2 viral oncogene homolog G12V mRNAKRAS G12V mRNA transcript

RNA interference (RNAi), antisense-mediated mRNA degradation, and translation of neoantigens for immunotherapy