A novel Listeria monocytogenes-based DNA delivery system for cancer gene therapy.
Authors
van Pijkeren, Jan PeterMorrissey, 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
2012-01-31T16:39:26ZMeSH
*Adenocarcinoma/genetics/microbiology/therapyAnimals
*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
Metadata
Show full item recordCitation
Hum Gene Ther. 2010 Apr;21(4):405-16.Journal
Human gene therapyDOI
10.1089/hum.2009.022PubMed ID
20105075Abstract
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
engISSN
1557-7422 (Electronic)1043-0342 (Linking)
ae974a485f413a2113503eed53cd6c53
10.1089/hum.2009.022
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