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The Marker of proliferation Ki-67 (Ki67) promoter is a DNA regulatory sequence that controls the expression of the MKI67 gene, a hallmark of cellular division (PMID: 10653597). In clinical practice, the Ki-67 protein is used to calculate the proliferation index of tumors, but its promoter is a key component in developing tumor-selective gene therapies (PMID: 12114471). By driving the expression of therapeutic genes—such as suicide genes like Herpes Simplex Virus thymidine kinase (HSV-TK)—specifically under this promoter, researchers can target malignant cells while sparing non-dividing healthy cells (PMID: 15610617). This approach, known as transcriptional targeting, is particularly useful in oncolytic virotherapy, where viral replication is restricted to Ki-67-positive cells (PMID: 19197323). Despite its specificity for proliferation, the promoter's activity in normal dividing tissues like the bone marrow and intestinal epithelium presents a significant safety challenge (PMID: 17438105). Clinical investigations have explored its utility in various cancers, including glioma and bladder carcinoma, often in combination with prodrugs like ganciclovir (PMID: 21151568). The promoter's strength and specificity continue to be optimized to improve the therapeutic window of these genetic interventions.
Transcriptional targeting where the Ki67 promoter drives the expression of therapeutic genes (e.g., suicide genes or viral replication genes) specifically in proliferating cells, allowing for selective destruction of tumor tissue.
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