Viral killer

The ability to selectively kill cells lacking normal p53 activity is an attractive anti-cancer strategy. In the August 30 Nature, Kenneth Raj and colleagues from the Swiss Institute for Experimental Cancer Research (ISREC) suggest that adeno-associated virus (AAV) could be employed as a 'hired assassin' (Nature 2001, 412:914-917). They found that AAV induced apoptosis of p53-deficient osteosarcoma cells, but induced cell-cycle arrest (in G2 phase) in cells expressing p53. None of the proteins encoded by the AAV genome was required for either of these effects; hairpin structures within the single-stranded viral genome induce a DNA-damage response that leads to apoptosis in the absence of functional p53. Raj et al. show that AAV can inhibit tumor growth in mouse models and suggest that viral delivery of DNA with unusual structures could be used to induce a DNA-damage response and cell death in the treatment human tumors that have lost p53 activity.