In vivo transfer of plasmid from food-grade transiting lactococci to murine epithelial cells

• Published in: Gene therapy Vol. 15; no. 16; pp. 1184 - 1190
• Main Authors: Chatel, J-M, Pothelune, L, Ah-Leung, S, Corthier, G, Wal, J-M, Langella, P
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2008; Nature Publishing Group
• Subjects: Allergens; Allergens - genetics; Allergens - immunology; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Applied cell therapy and gene therapy; Bacteria; Bacterial Translocation; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Biotechnology; Cattle; Cell Biology; Cellular biology; Cow's milk; Epithelial cells; Epithelial Cells - metabolism; Feces - chemistry; Female; Food; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene Therapy; Genetic aspects; Genetic Therapy - methods; Genetic transformation; Health aspects; Health. Pharmaceutical industry; Human Genetics; Immune response; Immunoglobulin A - analysis; Immunoglobulin E - analysis; Immunoglobulin G - analysis; Immunology; Industrial applications and implications. Economical aspects; Intestine, Small; Lactococcus; Lactococcus lactis; Lactococcus lactis - physiology; Lactoglobulins - genetics; Lactoglobulins - immunology; Life Sciences; Lymphocytes T; Mammalian cells; Medical sciences; Mice; Mice, Inbred BALB C; Milk Hypersensitivity - immunology; Milk Hypersensitivity - therapy; Models, Animal; Nanotechnology; Oral administration; original-article; Physiological aspects; Plasmids; Probiotics; Rodents; Small intestine; Th1 Cells - immunology; Th2 Cells - immunology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; β-Lactoglobulin; France; beta-lactoglobulin; lactococcus lactis; plasmid transfer; Lactococcus lactis; Rodentia; Plasmid; Streptococcaceae; In vivo; Vertebrata; Mammalia; Lactoglobulins; Mouse; Transfer; Bacteria; Micrococcales; Epithelial cell; Gene therapy
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/gt.2008.59

We recently demonstrated that noninvasive food-grade Lactococcus lactis (L. lactis) can deliver eukaryotic expression plasmid in mammalian cells in vitro . Here, we evaluated, in vivo , whether a eukaryotic expression plasmid carried by lactococci can translocate to the epithelial cells of the intestinal membrane. The strain LL(pLIG:BLG1) carrying one plasmid containing a eukaryotic expression cassette encoding β -lactoglobulin (BLG), a major allergen of cow's milk, was orally administered by gavage to mice. BLG cDNA was detected in the epithelial membrane of the small intestine of 40% of the mice and BLG was produced in 53% of the mice. Oral administration of LL(pLIG:BLG1) induced a low and transitory Th1-type immune response counteracting a Th2 response in case of further sensitization. We demonstrated for the first time the transfer of a functional plasmid to the epithelial membrane of the small intestine in mice by noninvasive food-grade lactococci.