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c-MET short hairpin RNA lentivirus is an experimental gene therapy agent designed to silence the expression of the c-MET (mesenchymal-epithelial transition) receptor, the high-affinity tyrosine kinase receptor for hepatocyte growth factor (HGF). Delivered via a lentiviral vector, the shRNA triggers RNA interference (RNAi) to degrade c-MET mRNA, leading to a significant reduction in c-MET protein levels. In the context of chronic lymphocytic leukemia (CLL), this knockdown disrupts the HGF/c-MET signaling axis, which normally promotes cell survival through the activation of AKT, ERK, and STAT3 pathways. The resulting inhibition of these pro-survival signals downregulates anti-apoptotic BCL-2 family proteins (such as BCL-2, MCL-1, and BCL-xL), arrests the cell cycle, and induces apoptosis in leukemic cells. This approach is being explored as a potential therapeutic strategy to overcome microenvironment-mediated drug resistance in CLL.
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