Figure 2.

Simplified scheme comparing the mechanism of replication of conditionally replicative ONYX in normal cells and neoplastic cells. (A) In normal cells, wild type adenoviruses replicate by blocking the normal activity of p53, a gene that, by inducing cell apoptosis, defends the host cell from viral infection. In order to exploit such function for targeted cancer therapy, researchers developed ONYX-015. ONYX-015 is a genetically engineered oncolytic adenovirus that preferentially replicates in neoplastic cells. It contains an 827-bp DNA deletion in the E1B region of the viral genome, which is responsible for the production of a mutant E1B-p55 protein. In normal cells, ONYX-015 induces a p53 response, leading to cell arrest and apoptosis, therefore preventing vector replication and contamination of non-cancer cells. (B) Cancer cells present a disrupted p53 pathway. Therefore, they are unable to suppress viral replication.