Generation of a conditionally replicating adenovirus harboring a P53-dependent self-destruction switch for treatment of P53-altered tumors

Background/aims: 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 concept exists that targets the viral vector DNA itself for selective destruction in normal cells. Here, we present an p53-dependent oncolytic adenovirus harboring a nuclease function for selective vector destruction in normal cells. Methods: We constructed conditionally-replicating adenoviruses expressing the meganuclease I-Sce I under control of a p53-dependent promoter. For targeted vector DNA destruction, the…