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The H19 imprinted maternally expressed transcript promoter is a regulatory DNA sequence that controls the expression of the H19 long non-coding RNA (lncRNA) (NCBI Gene ID: 2831). In normal physiology, H19 is highly expressed during fetal development but is largely silenced in most adult tissues, with the exception of certain specialized cells (PMID: 25633040). However, the H19 promoter becomes reactivated and highly potent in various human malignancies, including bladder, ovarian, and pancreatic cancers (PMID: 21475164). This tumor-specific activity makes the H19 promoter an attractive target for gene therapy, specifically through a strategy known as transcriptional targeting. Therapeutic agents like inodiftagene vultisene (BC-819) utilize the H19 promoter to drive the expression of a lethal toxin, such as Diphtheria toxin A, selectively within cancer cells (PMID: 31554158). By hijacking the cancer cell's own transcriptional machinery, this approach aims to induce apoptosis in malignant tissues while sparing healthy adult cells that do not express H19. Clinical development has primarily focused on non-muscle invasive bladder cancer, where the promoter's activity serves as both a trigger for therapy and a potential biomarker for patient selection.
Transcriptional targeting of cytotoxic gene expression
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