Methods to increase transgene expression from bacterial-based delivery systems by co-expressing suppressors of the eukaryotic type I interferon response
Bacterial delivery systems with improved transgene expression are provided. The recombinant bacterial delivery systems deliver transgenes of interest and suppressors of the eukaryotic Type I interferon response to eukaryotic cells. Suppression of the eukaryotic Type I interferon response allows improved expression of the encoded transgene.
1. A genetically engineered bacterium, comprising
nucleic acid sequences encoding
one or more passenger genes; and
one or more factors that inhibit a mammalian type I interferon response,
wherein
said nucleic acid sequences encoding said one or more passenger genes and said nucleic acid sequences encoding said one or more factors that inhibit a mammalian type I interferon response are operably linked to at least one eukaryotic promoter; or
said nucleic acid sequences encoding said one or more passenger genes are operably linked to a eukaryotic promoter and said nucleic acid sequences encoding said one or more factors that inhibit a mammalian type I interferon response are operably linked to a prokaryotic promoter.
2. The genetically engineered bacterium of claim 1 , wherein said nucleic acid sequences encoding said one or more factors that inhibit a mammalian type I interferon response are operably linked to a eukaryotic promoter.
3. The genetically engineered bacterium of claim 1 , wherein said nucleic acid sequences encoding said one or more factors that inhibit a mammalian type I interferon response are operably linked to a prokaryotic promoter.
4. The genetically engineered bacterium of claim 1 , wherein nucleic acid sequences encoding said one or more factors that inhibit a mammalian type I interferon response are present on a chromosome of said genetically engineered bacterium.
5. The genetically engineered bacterium of claim 1 , wherein one or both of:
i) nucleic acid sequences encoding said one or more passenger genes, and
ii) nucleic acid sequences encoding said one or more factors that inhibit a mammalian type I interferon response,
are present on a plasmid.
6. The genetically engineered bacterium of claim 1 , wherein said one or more factors that inhibit a type I mammalian interferon response are of viral origin.
7. The genetically engineered bacterium of claim 1 , wherein said one or more passenger genes encode tuberculosis antigens.
8. The genetically engineered bacterium of claim 1 , wherein said genetically engineered bacterium is a Shigella bacterium.
9. The genetically engineered bacterium of claim 1 , wherein said genetically engineered bacterium is a Mycobacterium.
10. The genetically engineered bacterium of claim 1 , wherein said one or more passenger genes is a heterologous transgene.