Transposon-based reprogramming to induced pluripotency

Abstract

Induced pluripotent stem (iPS) cells represent a recent innovation in the field of stem cells. Commonly, iPS cells are generated by viral transduction of core reprogramming genes, such as Oct4, Sox2, Klf4, c-Myc, Nanog and Lin28. However, integrating viruses, like retro- and lentiviral vectors, may cause insertional mutagenesis and may increase the risk of tumor formation. Therefore, alternative methods which avoid these safety concerns are intensively investigated. Here, we review the current status of transposon-based methods to induce pluripotency. DNA transposons are non-viral elements, which can be effectively integrated into a genome by their corresponding transposase enzyme. The advantages of transposon-based gene transfer are their increased safety, their large cargo capacity, their relatively simple design, and the availability of hyper-active and mutated transposase enzymes. For example, integration-deficient, excisioncompetent transposase variants allow the complete removal of the reprogramming transposon after successful reprogramming to obtain transposon-free reprogrammed cells. Transposon-based reprogramming broaden the toolbox for iPS cell production and will advance the establishment of safe, non-viral methods.