Replication-defective arenavirus vectors
AssigneeUniversitäT ZüRich
InventorsDaniel D. Pinschewer, Lukas Flatz, Andreas Bergthaler, Rolf Zinkernagel
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AssigneeUniversitäT ZüRich
InventorsDaniel D. Pinschewer, Lukas Flatz, Andreas Bergthaler, Rolf Zinkernagel
Estimating the term…
The invention relates to an infectious arenavirus particle that is engineered to contain a genome with the ability to amplify and express its genetic information in infected cells but unable to produce further infectious progeny particles in normal, not 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 allowing gene expression in arenavirus vector-infected cells, and foreign genes coding for an antigen or other protein of interest or nucleic acids modulating host gene expression are expressed under control of the arenavirus promoters, internal ribosome entry sites or under 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.
An infectious arenavirus particle engineered to contain a genome with the ability to amplify and express its genetic information in infected cells but unable to produce further infectious progeny particles in normal, not genetically engineered cells, wherein the arenavirus open reading frame glycoprotein (GP) is removed and replaced by a foreign ribonucleic acid sequence selected from short hairpin RNAs (shRNA), small interfering RNA (siRNA) and micro RNAs (miRNA).
An infectious arenavirus particle, wherein the arenavirus particle is engineered to contain a genome with the ability to amplify and express its genetic information in infected cells but unable to produce further infectious progeny particles in normal, not genetically engineered cells, wherein the arenavirus particle comprises a foreign ribonucleic acid sequence coding for an antigen selected from the group consisting of respiratory syncytial virus antigens, human immunodeficiency virus antigens, hepatitis C virus antigens, varizella zoster virus antigens, herpes simplex virus antigens, cytomegalovirus antigens and antigens derived from mycobacterium tuberculosis.
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