The discovery of induced pluripotent stem cells (iPSCs) has revolutionized the research platform for disease modeling, drug discovery, cell therapy and regenerative medicine. Due to the importance of iPSCs over the past decade, various studies have focused on finding a safe and efficient gene delivery system to introduce reprogramming factors (RFs) into somatic cells, particularly for clinical applications. However, generated iPSCs from any source must undergo genomic, epigenomic, and functional characterizations to ensure they are free of somatic memories and safe for clinical application.

In this review, almost all the employed cargos for delivering RFs into somatic cells were investigated, focusing on biological, chemical, and physical approaches to promote reprogramming efficiency and reduce exogenous factors. Moreover, the advantages and disadvantages of each approach were highlighted and cutting-edge technologies in iPSCs technology were also discussed. This review aims to provide a comprehensive overview discussing how to improve the efficiency and quality of iPSCs production.