INTERCELLULAR DELIVERY OF FUNCTIONAL P53 BY THE HERPESVIRUS PROTEIN VP22

The herpes simplex virus type 1 (HSV-1) virion protein VP22 exhibits t he remarkable property of intercellular trafficking whereby the protei n spreads from the cell in which it is synthesized to many surrounding cells. In addition to having implications for protein trafficking mec hanisms, this function of VP22 might be exploited to overcome a major hurdle in gene therapy, i.e., efficient delivery of genes and gene pro ducts. We show that chimeric polypeptides, consisting of VP22 linked t o the entire p53 protein, retain their ability to spread between cells and accumulate in recipient cell nuclei. Furthermore the p53-VP22 chi meric protein efficiently induces apoptosis in p53 negative human oste osarcoma cells resulting in a widespread cytotoxic effect. The interce llular delivery of functional p53-VP22 fusion protein is likely to pro ve beneficial in therapeutic strategies based on restoration of p53 fu nction. These results, demonstrating intracellular transport of large functional proteins, indicate that VP22 delivery may have applications in gene therapy.