Original Article

Gene Therapy advance online publication 17 April 2008; doi: 10.1038/gt.2008.59

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

J-M Chatel1,2,4, L Pothelune1,2, S Ah-Leung1,2, G Corthier3, J-M Wal1,2 and P Langella3

  1. 1Commissariat à l'Energie Atomique (CEA), Institut de Biologie et Technologies de Saclay (iBiTecS), Service de Pharmacologie et d'Immunologie, Gif-sur-Yvette, France
  2. 2Institut National de la Recherche Agronomique (INRA), Unité d'Immuno-Allergie Alimentaire, Domaine de Vilvert, Jouy en Josas cedex, France
  3. 3Institut National de la Recherche Agronomique (INRA), Unité d'Ecologie et Physiologie du Système Digestif, Domaine de Vilvert, Jouy en Josas cedex, France

Correspondence: Dr J-M Chatel, Institut National de la Recherche Agronomique, Commissariat à l'Energie Atomique, CE Saclay, SPI, Bat 136, Gif sur Yvette 91191, France. E-mail: jean-marc.chatel@jouy.inra.fr

4Current address: INRA-UEPSD, Domaine de Vilvert, 78352 Jouy-en-Josas, France

Received 5 December 2007; Revised 5 February 2008; Accepted 26 February 2008; Published online 17 April 2008.

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Abstract

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 beta-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.

Keywords:

lactococcus lactis, beta-lactoglobulin, plasmid transfer

Abbreviations:

LL, Lactococcus lactis MG1363; PBS, phosphate buffer saline; EIA, enzyme immuno assay

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