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Checkpoint kinase 1 (CHEK1) mRNA is the transcript encoding the CHEK1 protein, a vital serine/threonine kinase that regulates the cell cycle and DNA damage response (DDR) (NCBI Gene, 2024). The CHEK1 protein is primarily activated by ATR in response to single-stranded DNA breaks and replication stress, leading to the phosphorylation of CDC25 phosphatases and subsequent cell cycle arrest at the S and G2/M phases (UniProt, 2024). In the context of oncology, many tumors overexpress CHEK1 to survive high levels of replication stress and to bypass the loss of the G1 checkpoint, often due to TP53 mutations (Zhang et al., 2022). Targeting the CHEK1 mRNA using RNA interference (RNAi) or antisense oligonucleotides (ASOs) offers a method to deplete the protein levels entirely, thereby sensitizing cancer cells to chemotherapy and radiotherapy (Speroni et al., 2022). This strategy aims to induce 'mitotic catastrophe' by forcing cells with damaged DNA to enter mitosis prematurely. While small molecule inhibitors of the CHEK1 protein have reached clinical trials, mRNA-targeted therapies remain largely in the preclinical and early developmental stages, focusing on improving delivery systems like lipid nanoparticles (Di Francesco et al., 2022).
RNA interference (RNAi) or antisense-mediated degradation leading to the knockdown of Checkpoint kinase 1 protein expression.
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