# US 7,608,256 B2 · Methods to increase transgene expression from bacterial-based delivery systems by co-expressing suppressors of the eukaryotic type I interferon response

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- Number: US 7,608,256 B2
- Document ID: US7608256B2
- Status: Granted
- Kind: B2
- Application number: 11/854,027
- Filed: 2007-09-12
- Published: 2009-03-12
- Granted: 2009-10-27
- Earliest claimed: 2007-09-12
- Assignees: Aeras Global TB Vaccine Foundation
- Inventors: Jerald C. Sadoff; Mohamad F. Jamiluddin; Ravi P. Anantha; John F. Fulkerson, Jr.
- Web page: https://patentgrep.com/patent/US7608256B2

## CPC

- A61K 39/04: Mycobacterium, e.g. Mycobacterium tuberculosis
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 39/12: Viral antigens
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/04: Immunostimulants
- C12N 15/74: Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
- A61K 2039/523: {expressing foreign proteins}
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 1)

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.

### Claim 5 (depends on 1)

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.

### Claim 6 (depends on 1)

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.

### Claim 7 (depends on 1)

The genetically engineered bacterium of claim 1, wherein said one or more passenger genes encode tuberculosis antigens.

### Claim 8 (depends on 1)

The genetically engineered bacterium of claim 1, wherein said genetically engineered bacterium is a Shigella bacterium.

### Claim 9 (depends on 1)

The genetically engineered bacterium of claim 1, wherein said genetically engineered bacterium is a Mycobacterium.

### Claim 10 (depends on 1)

The genetically engineered bacterium of claim 1, wherein said one or more passenger genes is a heterologous transgene.