Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) allows 
the derivation of -personalized stem cells. Transposon transgenesis is a novel 
and viable alternative to viral transduction methods for the delivery of 
reprogramming factors (Oct4, Sox2, Klf4, c-Myc) to somatic cells. Since 
transposons can be introduced as naked DNA using common plasmid transfection 
protocols, they provide a safer alternative to viral methods. piggyBac 
transposons are host-factor independent and integrate stably into the target 
genome, yet benefit from the unique characteristic of seamless removal mediated 
by transient expression of piggyBac transposase. Thus, piggyBac transposition 
provides an effective means to generate human, transgene-free iPSCs. The 
protocol describes the production of iPSCs from human embryonic fibroblasts, 
delivering reprogramming factors via plasmid transfection and piggyBac 
transposition.