Here, we explored the use of serotype 5 adenoviruses (Ad5) engineered 1) to sequester overexpressed HMGA1 in cancer cells using an HMGA1 hyper binding site (HBS) inserted into the Ad5 genome and 2) to suppress HMGA1 synthesis in cancer cells by incorporating exogenous genes into the Ad5 genome that encode an artificial HMGA1 cis-antisense transcript (AAT) and that encode a gene to express an HMGA1-targeted shRNA transcript (shRNA). This evidence concerns the gene HMGA1 and cancer.