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Chk1 siRNA is a small interfering RNA (siRNA) designed to silence the expression of Checkpoint kinase 1 (Chk1), a serine/threonine kinase that plays a central role in the DNA damage response (DDR). Chk1 is essential for the activation of cell cycle checkpoints (S and G2/M) in response to genotoxic stress, allowing time for DNA repair. By mediating the degradation of Chk1 mRNA, Chk1 siRNA abrogates these checkpoints, leading to premature mitotic entry, genomic instability, and apoptosis, particularly in p53-deficient cells. This approach is widely used in preclinical research to sensitize various cancer types—including pancreatic, colorectal, and lung cancers—to DNA-damaging chemotherapies such as gemcitabine and 5-fluorouracil. Some research has also explored covalent siRNA-gemcitabine constructs to ensure co-delivery of the synergistic agents to the same tumor cells.
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