ARENA REPLICA DEFECTIVE VARIANT

Abstract

The invention relates to an infectious arenavirus particle that is genetically engineered to contain a genome with the ability to amplify and express its genetic information in infected cells but incapable of producing further infectious progeny particles in normal, non-genetically engineered cells.One or more of the four arenavirus open reading frames glycoprotein (GP), nucleoprotein (NP), matrix protein Z, and RNA-dependent RNA polymerase L are removed or mutated to prevent replication in normal cells, but still allow gene expression in arenavirus vector-infected cells, and foreign genes encoding an antigen or other protein of interest or nucleic acids that regulate host gene expression are expressed under the control of arenavirus promoters, internal ribosome entry sites, or under the control of regulatory elements that can be read by the viral RNA-dependent RNA polymerase, cellular RNA polymerase I, RNA polymerase II, or RNA polymerase III. The modified arenaviruses are useful as vaccines and therapeutic agents for a variety of diseases.