Specialists from the Yong Loo Lin School of Medicine, operating at the National University of Singapore, have created an improved RNA therapy method. Its target is KRAS, one of the most treatment-resistant oncogenes with defective characteristics. A report on this scientific work was published in the journal Theranostics. The KRAS gene, functioning like a molecular switch, controls cell growth and proliferation processes. When mutations occur in it, KRAS initiates uncontrolled cell reproduction, which in turn leads to the development of neoplasms and enhances their ability to evade immune surveillance. Such genetic changes are found in a significant proportion of patients suffering from pancreatic, lung, and colorectal cancer. The scientists developed a strategy combining the action of two types of biologically active molecules. The first element is antisense oligonucleotides; these are short segments of nucleic acids designed to interfere with the expression of a specific gene, thereby preventing the synthesis of the mutated KRAS protein. The second component is an RNA molecule that modifies the immune response by activating the RIG-I signaling cascade, which is typically triggered by viral invasion and elicits a powerful body defense. The delivery of both molecules into the body is achieved using extracellular vesicles—microscopic bubbles derived from blood cells (erythrocytes). In laboratory tests, the combination therapy simultaneously blocked KRAS’s potential to induce oncogenesis and stimulated antiviral immune pathways. This led to the transformation of so-called “cold” tumors, invisible to the immune system, into “hot” tumors, which become recognizable and attacked by immune cells. As a result, a reduction in tumor mass and increased survival were observed in the test animals without causing harm to healthy tissues. The authors of the study believe that this innovative approach could serve as a foundation for developing treatments for various cancers associated with mutations in the KRAS gene. However, before commencing clinical trials in humans, this method requires further validation.
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