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AssigneeThe Regents of the University of California
InventorsRaul Andino-Pavlovsky, Marco Vignuzzi, Derek H. Wells
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The present invention provides a live, attenuated, invasive bacterium that infects a mammalian host cell, and releases exogenous RNA into the cytoplasm of the host cell. The present invention further provides compositions, including immunogenic compositions, comprising a subject bacterium. The present invention provides methods of delivering an RNA to a eukaryotic host cell in vitro, ex vivo, or in vivo. The present invention provides methods of delivering a protein to a host cell in vitro, ex vivo, or in vivo. The present invention provides methods of controlling expression of a target gene in a eukaryotic host cell. The present invention provides methods of inducing an immune response in a mammalian host to a polypeptide antigen, the method involving administering to the host a subject bacterium, wherein the antigen is encoded by the exogenous RNA produced by the bacterium.
A bacterial delivery system comprising a live, attenuated bacterium comprising a DNA expression vector, which DNA expression vector comprises a nucleotide sequence encoding an exogenous RNA, wherein the nucleotide sequence is operably linked to a heterologous promoter that is functional in the bacterium, wherein said bacterium synthesizes the exogenous RNA encoded by the DNA vector, wherein the bacterium comprises an asd mutation, resulting in an impaired ability to synthesize a cell wall component, and an orgA mutation, resulting in reduced ability to induce apoptosis in the host eukaryotic cell, wherein the bacterium is a Salmonella strain, a Shigella strain, an Eseherichia coli strain, a Rickettsia strain, or a Listeria strain, and wherein, following infection of a eukaryotic host cell, the bacterium releases the exogenous RNA into the cytoplasm of the eukaryotic host cell.
A bacterial delivery system comprising a live, attenuated bacterium comprising a DNA expression vector, which DNA expression vector comprises a nucleotide sequence encoding an exogenous RNA, wherein the exogenous RNA is an infectious recombinant viral RNA, wherein the nucleotide sequence is operably linked to a heterologous promoter that is functional in the bacterium, wherein said bacterium synthesizes the exogenous RNA encoded by the DNA vector, wherein the bacterium is a Salmonella strain, a Shigella strain, an Eseherichia coli strain, a Rickettsia strain, or a Listeria strain, and wherein, following infection of a eukaryotic host cell, the bacterium releases the exogenous RNA into the cytoplasm of the eukaryotic host cell.
Dependencies are inferred from the claim text.