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The wild-type hTERT promoter oligonucleotide is a synthetic G-rich oligonucleotide designed to target the promoter region of the human telomerase reverse transcriptase (hTERT) gene. In many cancers, particularly malignant melanoma, the hTERT promoter frequently contains mutations that destabilize the formation of inhibitory G-quadruplex DNA structures, leading to constitutive telomerase expression and cellular immortality. This oligonucleotide therapy acts by binding to the complementary C-rich strand of the genomic DNA through strand invasion and Watson-Crick base pairing. This interaction stabilizes the G-quadruplex structure in the promoter region, effectively silencing hTERT transcription and inhibiting tumor cell proliferation. The approach was developed by researchers at the University of Louisville as a novel strategy to overcome the transcriptional activation caused by common promoter mutations.
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