**1. Introduction**

#### **1.1. Concept of genetically engineered microorganisms as delivery vectors**

Although significant progress has been made in physical and chemical methods for gene delivery, these nonmicrobial strategies still present some drawbacks related to specificity and efficiency of gene transfer [1–6]. For example, new formulations of lipid nanoparticles have led to great improvement in gene stability and transfer, yet there remains a lack of a targeting system that would favor the gene transfer to particular cell tissues [7]. Live avirulent microbial vectors such as viruses and bacteria are a promising approach for gene delivery that may serve

© 2015 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

to fill in those blanks [8–14]. As such, microbial vectors are able to not only serve as cell factories for the production of the transgene but also as vehicles that deliver the transgene to specific cells for which they have a naturally high tropism. Gene transduction with recombinant viruses is generally based on the use of an expression cassette encompassing a transgene [8– 11], while in bacteria, the classic approach of gene transfer is based on plasmid-encoded genes [12–14]. The gene of interest must be delivered to the cell's nucleus to allow an efficient manufacturing of the corresponding protein. DNA escape from intracellular bacteria to host cell cytosol may occur following their phagocytosis and lysosomal degradation within the cell. This is, however, not the case for intracellular bacteria that resist or subvert the phagolysosomal processing such as *Salmonella* or *Listeria* [15,16] and for extracellular bacteria that behave as commensals within a specific cellular niche. Commensal bacteria might be, however, of particular interest if the treatment strategy aims at delivering a gene product to targeted cell tissue through a potent delivery machinery. The delivery system used by avirulent vectors is therefore a critical point for optimizing the success of any therapy.
