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Ad312-E1A is a recombinant, conditionally replicative oncolytic adenovirus (CRAd) designed for the selective treatment of colorectal cancer. It exploits the epigenetic phenomenon of Loss of Imprinting (LOI) of the insulin-like growth factor 2 (IGF2) gene, which is frequently observed in malignant cells but not in normal tissues. The virus is engineered to express the essential adenoviral E1A protein under the control of regulatory sequences that are activated specifically in cells with IGF2 LOI. This selective expression drives viral replication and subsequent lysis of the host cancer cell. Preclinical studies have demonstrated that Ad312-E1A induces apoptosis and inhibits tumor growth in IGF2 LOI-positive colorectal cancer cell lines (such as HCT-8 and HT-29) and xenograft models, while showing minimal activity in cells with normal imprinting.
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