In detail, majority of the newer human serotype 5 oAd constructs, like ONCOS-102, LoAd703, TILT-123, ORCA-010, CG0070, under active clinical development contain intact E1B 55 kDa gene to circumvent the attenuation in viral replication capacity, and rather employ different genetic engineering strategies like cancer-specific promoter driven Ad E1A expression or deletion of the Rb binding site in Ad E1A gene to achieve preferential replication in cancer cells (33–38). The gene discussed is DHTKD1; the disease is cancer.