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H19-DTA-P4-DTA is a double promoter plasmid-based gene therapy vector designed for the targeted treatment of various human cancers. The construct contains two separate expression cassettes: one where the diphtheria toxin A-fragment (DTA) is under the control of the H19 promoter, and another where DTA is controlled by the IGF2-P4 promoter. These promoters are oncofetal regulatory sequences that are highly active in tumor cells but nearly undetectable in normal adult tissues. Upon entering a cancer cell, the plasmid drives the intracellular production of DTA, which inhibits protein synthesis by ADP-ribosylating elongation factor 2 (EF-2), leading to selective apoptosis of the malignant cells. This 'double promoter' strategy is intended to increase the breadth and efficacy of the therapy by targeting cells that express either or both of these cancer-specific markers, overcoming tumor heterogeneity and providing superior anti-cancer activity compared to single-promoter vectors.
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