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

Human Gene Therapy
Jan Peter van PijkerenMark Tangney

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) systemi...Continue Reading

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Citations

Sep 22, 2012·Cancer Gene Therapy·M CroninM Tangney
Apr 15, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Michelle CroninMark Tangney
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Jan 22, 2021·Life Sciences·Esam Bashir Yahya, Amaal Mohammed Alqadhi
May 4, 2021·Frontiers in Immunology·Mariam OladejoLaurence M Wood

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Methods Mentioned

BETA
PCR
transfection
flow cytometry
FACS
transfect

Software Mentioned

Living Image
BD FACSDiva

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