A primary limitation to using nonviral vectors for cancer gene therapy is transient expression of the therapeutic gene. Even when the ultimate goal is tumor cell death, a minimum threshold of gene expression is required to kill tumor cells by direct or indirect mechanisms. It has been shown that transposable elements can significantly enhance the duration of gene expression when plasmid DNA vectors are used to transfect tumor or tumor-associated stroma. Much like a retrovirus, transposon-based plasmid vectors achieve integration into the genome, and thereby sustain transgene expression, which is especially important in actively mitotic cells such as tumor cells. Herein we briefly discuss the different transposons available for gene therapy applications, and provide a detailed protocol for nonviral transposon-based gene delivery to solid experimental tumors in mice.
