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

Hdl Handle:
http://hdl.handle.net/10147/206381
Title:
A novel Listeria monocytogenes-based DNA delivery system for cancer gene therapy.
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.
Citation:
Hum Gene Ther. 2010 Apr;21(4):405-16.
Journal:
Human gene therapy
Issue Date:
31-Jan-2012
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
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
ISSN:
1557-7422 (Electronic); 1043-0342 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorvan Pijkeren, Jan Peteren_GB
dc.contributor.authorMorrissey, Daviden_GB
dc.contributor.authorMonk, Ian Ren_GB
dc.contributor.authorCronin, Michelleen_GB
dc.contributor.authorRajendran, Simonen_GB
dc.contributor.authorO'Sullivan, Gerald Cen_GB
dc.contributor.authorGahan, Cormac G Men_GB
dc.contributor.authorTangney, Marken_GB
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.en_GB
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-

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