ed into many of the same carriers that can be used for siRNA delivery, although the nature of the particle will change with the different cargo (large DNAs versus small RNAs). Several non-viral platforms for gene delivery are being investigated (reviewed in Ref. [@CR71]) and, as for siRNAs, commercial reagents are available for plasmid transfection of cell lines and some primary cells *in vitro*.

Bacteria can be used as an innovative platform for RNAi delivery; this approach is built on earlier work showing that therapeutic bacteria can enter tumours in patients with cancer^[@CR72]^, presumably via a permissive vasculature. The basic premise is that recombinantly engineered *Escherichia coli* can enter mammalian cells after *in vivo* delivery and transfer shRNAs. When bacteria containing plasmids that expressed shRNAs targeting β-catenin were fed to mice, β-catenin expression was reduced in the intestinal epithelium^[@CR73]^. This platform is now in clinical testing for familial adenomatous polyposis, an inherited form of colon cancer^[@CR74]^. A related approach in mice used [minicells](#Glos10){ref-type="list"} derived from *Salmonella enterica* subsp. *enterica* serovar Typhimurium and targeted them to tumour-cell-surface receptors to deliver siRNAs or shRNAs; this method reduced tumour burden and improved mouse survival^[@CR75]^.

***Delivery systems: viral vectors***. The viral vectors used to deliver shRNAs or artificial miRNAs include murine oncoretroviruses, lentiviruses, adenoviruses, [adeno-associated viruses](#Glos11){ref-type="list"} (AAVs), and herpesviruses, among others ([Table 2](#Tab2){ref-type="table"}). We refer the reader to recent reviews describing the biology and production of these vector systems^[@CR76],[@CR77],[@CR78],[@CR79],[@CR80]^. Here we highlight major differences among some of the tools that are relevant to their use for RNAi-based applications, with respect to their tissue tropisms and the fate of their recombinant genomes in host cells.

The genomes of recombinant adenovirus