Generation of a conditionally replicating adenovirus harboring a p53-dependent self-destruction switch for treatment of p53-altered tumors

Conditionally replicating adenoviruses represent a promising approach for the treatment of solid tumors. Actual concepts focus on restricting viral replication to malignant cells but no concepts exist that selectively target the vector DNA for destructions in normal cells. In this study we present conditioned oncolytic adenoviruses harboring a nuclease function for seIective vector destruction in p53-normal cells. We constructed Adenoviruses that express the yeast meganuclease I-Sce I under control of the p53-dependent promoter prMin-RGC. To achieve susceptibility for targeted destruction, viral early genes (E1A…