Bristol-myers Squibb Compnay

Fox Chase Cancer Center

Avid Therapeutics, Inc.

Robert W King

Christoph Seeger

Claudio Pasquinelli

Matthew W Jeffries

Christopher S Barker

An in vitro method to conduct genomic replication of the viral genomes of viruses that utilize RNA-dependent RNA polymerase for replication (RDRP viruses), such as HCV. The method employs a construct comprising the 3&prime; and 5&prime; untranslated regions (UTRs) of the viral genome which are operably linked on the 5&prime; and 3&prime; ends of a reporter sequence, in antisense orientation, such that when viral replication is occurring within the cell which produces RDRP, the reporter protein will be made. The method of the invention provides an efficient means for measuring genomic replication in RDRP viruses, and also for the rapid screening of compounds for their ability to inhibit genomic replication of RDRP viruses, including the Hepatitis C virus (HCV).

In vitro system for replication of RNA-dependent RNA polymerase (RDRP) viruses

Novel cell lines and methods are provided for inducibly expressing the Hepatitis B virus (HBV) genome within cultured cells. Cells are stably transformed with an HBV genome under control of an operator/promoter target sequence which can activate expression of the HBV genome when bound by a cognate transactivator protein. The cell lines are also stably transformed with a gene that encodes and expresses a suitable transactivator protein. Cells may be maintained under non-inducing conditions whereby the transactivator protein is unable to interact with the operator/promoter target sequence, so the HBV genome is not expressed. Under appropriate inducing conditions, the transactivator protein is enabled to interact with the operator/promoter target sequence, thereby activating expression of the HBV genome. The inducible system provides an effective and rapid cell-based assay to screen compounds for anti-hepadnaviral activity.

Cultured cell line that inducibly expresses the hepatitis B virus

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West Chester, PA, United States of America

Robert W King