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AssigneeInstitut Fur Viruskrankheiten Und Immunprophylaxe
InventorsJon Duri Tratschin, Nicolas Ruggli, Kenneth Charles McCullough
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Replicons of pestiviruses, in particular replicons of swine fever virus, are engineered to have a defective replication thereby having lost infectivity, and further containing a foreign gene. A replicon contains all the genetic information required for its replication, but lacks essential codons or all codons of at least one of the genes encoding the viral structural proteins E1, E2, Ems or C protein, and consequently cannot generate infectious virus particles. Particular replicons are generated with a mutated gene encoding a modified Npro protein that no longer controls the cell interferon-induction pathway. Another particular replicon lacks the genes encoding all the structural proteins, the p7 protein and the NS2 protein, and has cytopathogenic properties in transduced cells. The replicons provide a new vector system that can be used for vaccination, gene delivery and gene therapy applications in mammals, including humans, as naked RNA or packaged into any form of delivery vehicle.
A method of prophylaxis against a disease caused by an infectious agent, the method comprising administering to a mammal a composition comprising a particulate delivery vehicle comprising a single-stranded RNA pestivirus replicon lacking essential codons or all codons for one or more structural proteins required for formation of infectious virus, and carrying a foreign gene encoding a gene product immunizing against the infectious agent or the disease-causing moiety, wherein the single-stranded RNA pestivirus replicon is encapsulated inside the particulate delivery vehicle to protect the single-stranded RNA pestivirus replicon against RNase degradation and wherein the particulate delivery vehicle is appropriate to deliver the single-stranded RNA pestivirus replicon to the cytoplasm of cells for replication and translation of the single-stranded RNA pestivirus replicon in the cytoplasm.
A pharmaceutical composition comprising a particulate delivery vehicle comprising a single-stranded RNA pestivirus replicon lacking essential codons or all codons for one or more structural proteins required for formation of infectious virus, and carrying a foreign gene encoding a gene product immunizing against the infectious agent or the disease-causing moiety, wherein the single-stranded RNA pestivirus replicon is encapsulated inside the particulate delivery vehicle to protect the single-stranded RNA pestivirus replicon against RNase degradation and wherein the particulate delivery vehicle is appropriate to deliver the single-stranded RNA pestivirus replicon to the cytoplasm of cells for replication and translation of the single-stranded RNA pestivirus replicon in the cytoplasm.
Dependencies are inferred from the claim text.