Kirsten rat sarcoma viral oncogene homolog mRNA (KRAS)

The KRAS (Kirsten rat sarcoma viral oncogene homolog) gene encodes a small GTPase protein that functions as a critical molecular switch in intracellular signaling pathways, including the RAS/MAPK and PI3K/AKT cascades (UniProt P01116). These pathways are fundamental to the regulation of cell growth, differentiation, and survival (MedlinePlus). Mutations in the KRAS nucleic acid sequence, particularly at hotspot codons such as G12, G13, and Q61, lead to the production of a constitutively active protein that drives oncogenesis in approximately 25% of all human cancers (Wikipedia). Targeting the KRAS-specific nucleic acid sequence, primarily the messenger RNA (mRNA), represents a potent therapeutic strategy to silence the expression of this historically "undruggable" oncoprotein (MDPI). Modalities such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are designed to bind complementarily to the KRAS transcript, leading to its degradation or the inhibition of translation (PNAS). Additionally, mRNA-based vaccines are being developed to encode mutant KRAS epitopes, thereby priming the host immune system to recognize and eliminate cancer cells (NIH). Despite the promise of these nucleic acid-based approaches, significant challenges remain, including the need for efficient systemic delivery systems and the potential for off-target effects on wild-type KRAS signaling (PNAS).

Other names

KRAS mRNAKRAS transcriptKRAS-specific nucleic acid sequenceKirsten rat sarcoma viral oncogene homolog genec-K-ras mRNA

RNA interference (siRNA), RNase H-mediated mRNA degradation (ASO), translation inhibition, and induction of tumor-specific T-cell responses (mRNA vaccines)