Transposons for Non-Viral Gene Transfer

DNA based transposon vectors offer a mechanism for non-viral gene delivery into mamma‐ lian and human cells. These vectors work via a cut-and-paste mechanim whereby transpo‐ son DNA containing a transgene(s) of interest is integrated into chromosomal DNA by a transposase enzyme. The first DNA based transposon system which worked efficienty in human cells was sleeping beauty. This was followed a few years later by the use of the piggy‐ Bac transposon system in mammalian and human cells. The advantages of transposon vec‐ tors include lower cost, less innate immunogenicity, and the ability to easily co-deliver multiple genes when compared to viral vectors. However, when compared to viral vectors, non-viral transposon systems are limited by delivery to cells, they are possibly still immuno‐ genic, and they can be less efficient depending on the cell type of interest. Nonetheless, transposons have shown promise in genetic modification of clinical grade cell types such as human T lymphocytes, induced pluripotent stem cells, and stem cells. Recently generated hyperactive transposon elements have improved gene delivery to levels similar to that ob‐ tained with viral vectors. In addition, current research is focused on manipulating transpo‐ son systems to achieve user-selected and site-directed genomic integration of transposon DNA cargo to improve safety and efficacy of transgene delivery. DNA based transposon systems represent a powerful tool for gene therapy and genome engineering applications.