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Figure 1: The current approaches of iPSC generation. There are a number of different approaches for iPSC generation from somatic cell reprogramming, including gene transduction and integration-free methods. Retroviral or lentiviral gene transduction is the most efficient and widely used method, but the integration of TFs into a host genome increases the concerns of oncogenicity and mutagenesis. The integration-free methods include using nonintegrating virus, plasmids, recombinant proteins, synthesized mRNA, microRNAs, and small molecules. Most of these approaches are safe, but reprogramming efficiency is lower than that of gene integration. The activation of endogenous pluripotency is considered an important criterion of high-quality fully reprogrammed iPSCs.