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dc.contributor.authorvan Pijkeren, Jan Peter
dc.contributor.authorMorrissey, David
dc.contributor.authorMonk, Ian R
dc.contributor.authorCronin, Michelle
dc.contributor.authorRajendran, Simon
dc.contributor.authorO'Sullivan, Gerald C
dc.contributor.authorGahan, Cormac G M
dc.contributor.authorTangney, Mark
dc.date.accessioned2012-01-31T16:39:26Z
dc.date.available2012-01-31T16:39:26Z
dc.date.issued2012-01-31T16:39:26Z
dc.identifier.citationHum Gene Ther. 2010 Apr;21(4):405-16.en_GB
dc.identifier.issn1557-7422 (Electronic)en_GB
dc.identifier.issn1043-0342 (Linking)en_GB
dc.identifier.pmid20105075en_GB
dc.identifier.doi10.1089/hum.2009.022en_GB
dc.identifier.urihttp://hdl.handle.net/10147/206381
dc.description.abstractBacteria-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.
dc.language.isoengen_GB
dc.subject.mesh*Adenocarcinoma/genetics/microbiology/therapyen_GB
dc.subject.meshAnimalsen_GB
dc.subject.mesh*Breast Neoplasms/genetics/microbiology/therapyen_GB
dc.subject.meshCaco-2 Cells/microbiologyen_GB
dc.subject.meshCell Line, Tumoren_GB
dc.subject.meshDNA, Bacterial/geneticsen_GB
dc.subject.meshFemaleen_GB
dc.subject.mesh*Gene Transfer Techniquesen_GB
dc.subject.meshGenetic Vectors/*administration & dosage/genetics/metabolismen_GB
dc.subject.meshHumansen_GB
dc.subject.meshListeria monocytogenes/*genetics/pathogenicityen_GB
dc.subject.meshListeriosis/microbiologyen_GB
dc.subject.meshLuciferases/genetics/metabolismen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Inbred BALB Cen_GB
dc.subject.meshMice, Nudeen_GB
dc.subject.meshPlasmids/*geneticsen_GB
dc.titleA novel Listeria monocytogenes-based DNA delivery system for cancer gene therapy.en_GB
dc.contributor.departmentCork Cancer Research Centre, Mercy University Hospital and Leslie C. Quick Jnr., Laboratory, University College Cork, Cork, Ireland.en_GB
dc.identifier.journalHuman gene therapyen_GB
dc.description.provinceMunster
html.description.abstractBacteria-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.


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