The use of Listeria monocytogenes as a DNA delivery vector for cancer gene therapy

Abstract

Addendum to: van Pijkeren JP, Morrissey D, Monk IR, Cronin M, Rajendran S, O’Sullivan GC, Gahan CGM, Tangney M. A novel Listeria monocytogenes-based DNA delivery system for cancer gene therapy. Human Gene Therapy 2010; 21 Listeria monocytogenes is an intracellular pathogen that lyses the phagosomal vacuole of infected cells, proliferates in the host cell cytoplasm and can actively enter adjacent cells. The pathogen is therefore well suited to exploitation as a vector for the delivery of DNA to target cells as the lifecycle favours cellular targeting with vector amplification and the potential for cell-to-cell spread. We have recently demonstrated DNA transfer by L. monocytogenes in growing tumors in murine models. Our approach exploited an ampicillin sensitive stain of L. monocytogenes which can be lysed through systemic administration of ampicillin to facilitate release of plasmid DNA for expression by infected mammalian cells. Here, we discuss the implications of this technology and the potential for future improvements of the system.