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AssigneeSt. Jude Children's Research Hospital
InventorErich Hoffmann
Estimating the term…
The present invention is based on the development of a dual promoter system (preferably a RNA pol I-pol II system) for the efficient intracellular synthesis of viral RNA. The resultant minimal plasmid-based system may be used to synthesize any RNA virus, preferably viruses with a negative single stranded RNA genome. The viral product of the system is produced when the plasmids of the system are introduced into a suitable host cell. One application of the system is production of attenuated, reassortant influenza viruses for use as antigens in vaccines. The reassortant viruses generated by cotransfection of plasmids may comprise genes encoding the surface glycoproteins hemagglutinin and neuraminidase from an influenza virus currently infecting the population and the internal genes from an attenuated influenza virus. An advantageous property of the present invention is its versatility; the system may be quickly and easily adapted to synthesize an attenuated version of any RNA virus. Attenuated or inactivated RNA viruses produced by the present invention may be administered to a patient in need of vaccination by any of several routes including intranasally or intramuscularly.
An expression plasmid comprising an RNA polymerase I (pol I) promoter and pol I terminator sequences, which are inserted between an RNA polymerase II (pol II) promoter and a polyadenylation signal.
A minimum plasmid-based system for the generation of infectious negative strand RNA viruses from cloned viral cDNA comprising a set of plasmids wherein each plasmid comprises one autonomous viral genomic segment, and wherein the viral cDNA corresponding to the autonomous viral genomic segment is inserted between an RNA polymerase I (pol I) promoter and terminator sequences, thereby resulting in expression of vRNA, which are in turn inserted between a RNA polymerase II (pol II) promoter and a polyadenylation signal, thereby resulting in expression of viral mRNA.
A composition comprising a negative strand RNA virus virion, wherein viral internal proteins of the virion are from a virus strain well adapted to grow in culture or from an attenuated Strain or both and viral antigen proteins, of the virion are from a pathogenic virus strain.
Dependencies are inferred from the claim text.