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    A novel Listeria monocytogenes-based DNA delivery system for cancer gene therapy.

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    Authors
    van Pijkeren, Jan Peter
    Morrissey, David
    Monk, Ian R
    Cronin, Michelle
    Rajendran, Simon
    O'Sullivan, Gerald C
    Gahan, Cormac G M
    Tangney, Mark
    Affiliation
    Cork Cancer Research Centre, Mercy University Hospital and Leslie C. Quick Jnr., Laboratory, University College Cork, Cork, Ireland.
    Issue Date
    2012-01-31T16:39:26Z
    MeSH
    *Adenocarcinoma/genetics/microbiology/therapy
    Animals
    *Breast Neoplasms/genetics/microbiology/therapy
    Caco-2 Cells/microbiology
    Cell Line, Tumor
    DNA, Bacterial/genetics
    Female
    *Gene Transfer Techniques
    Genetic Vectors/*administration & dosage/genetics/metabolism
    Humans
    Listeria monocytogenes/*genetics/pathogenicity
    Listeriosis/microbiology
    Luciferases/genetics/metabolism
    Mice
    Mice, Inbred BALB C
    Mice, Nude
    Plasmids/*genetics
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    Metadata
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    Citation
    Hum Gene Ther. 2010 Apr;21(4):405-16.
    Journal
    Human gene therapy
    URI
    http://hdl.handle.net/10147/206381
    DOI
    10.1089/hum.2009.022
    PubMed ID
    20105075
    Abstract
    Bacteria-mediated transfer of plasmid DNA to mammalian cells (bactofection) has been shown to have significant potential as an approach to express heterologous proteins in various cell types. This is achieved through entry of the entire bacterium into cells, followed by release of plasmid DNA. In a murine model, we show that Listeria monocytogenes can invade and spread in tumors, and establish the use of Listeria to deliver genes to tumors in vivo. A novel approach to vector lysis and release of plasmid DNA through antibiotic administration was developed. Ampicillin administration facilitated both plasmid transfer and safety control of vector. To further improve on the gene delivery system, we selected a Listeria monocytogenes derivative that is more sensitive to ampicillin, and less pathogenic than the wild-type strain. Incorporation of a eukaryotic-transcribed lysin cassette in the plasmid further increased bacterial lysis. Successful gene delivery of firefly luciferase to growing tumors in murine models and to patient breast tumor samples ex vivo was achieved. The model described encompasses a three-phase treatment regimen, involving (1) intratumoral administration of vector followed by a period of vector spread, (2) systemic ampicillin administration to induce vector lysis and plasmid transfer, and (3) systemic administration of combined moxifloxacin and ampicillin to eliminate systemic vector. For the first time, our results reveal the potential of Listeria monocytogenes for in vivo gene delivery.
    Language
    eng
    ISSN
    1557-7422 (Electronic)
    1043-0342 (Linking)
    ae974a485f413a2113503eed53cd6c53
    10.1089/hum.2009.022
    Scopus Count
    Collections
    Mercy University Hospital

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