Microrna mediated oncolytic targeting

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 7/01 (2006.01) A61K 35/76 (2006.01) A61K 48/00 (2006.01) A61P 35/00 (2006.01) C12N 15/11 (2006.01) C12N 15/86 (2006.01)

Patent

CA 2625811

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 non0cancerous 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.

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