MICRORNA MEDIATED ONCOLYTIC TARGETING

摘要

The invention provides methods for preferentially killing target cells in a host by infecting the cells with one or more strains of a lytic virus that has been engineered to be susceptible to microRNA mediated translational repression. Methods of the invention thereby exploit differential microRNA expression in target and non-target cells of the host. For example, altered expression of microRNAs in cancer cells can be exploited to alter expression of a viral gene in cancer cells, compared to non-cancerous cells, to achieve tumour specific replication of an engineered virus, such as a vesicular stomatitis virus (VSV). In a selected embodiment, incorporation of let-7a microRNA complementary sequences within the VSV genome attenuates viral replication and associated toxicity in normal cells, but permits growth in cancer cells.