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Vascular endothelial growth factor receptor 2 (VEGFR2) mRNA, also known as KDR mRNA, is the transcript that encodes the primary receptor responsible for mediating the effects of vascular endothelial growth factor (VEGF) on angiogenesis and vascular permeability (UniProt P35968). This mRNA is highly expressed in vascular endothelial cells, particularly during periods of active vessel growth such as embryonic development or tumor-induced neo-angiogenesis (PubMed: 19147529). In various cancers, the upregulation of VEGFR2 mRNA leads to increased receptor density on the cell surface, which promotes tumor survival, growth, and metastasis by ensuring an adequate blood supply (PubMed: 22547154). Unlike traditional therapies that target the VEGFR2 protein with antibodies or small molecule inhibitors, RNA-based therapeutics target the mRNA itself to prevent protein synthesis. For instance, the drug candidate ALN-VSP utilizes lipid nanoparticle-encapsulated small interfering RNAs (siRNAs) to trigger the degradation of VEGFR2 mRNA via the RNA-induced silencing complex (RISC) (NCT00882180). This approach aims to achieve more comprehensive inhibition of the VEGF pathway by reducing the total expression of the receptor, potentially bypassing certain resistance mechanisms encountered by protein-level inhibitors.
RNA interference (RNAi) mediated mRNA degradation and antisense-mediated translational inhibition
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