Full utilization of iPSCs for personalized medicine and disease modeling requires the development of methods of efficient genetic modification including gene targeting and efficient expression or reporters. Recently, it has been shown that gene targeting in iPSCs can be achieved by homologous recombination mediated by zinc finger nucleases [22,23]. Efficient gene transfer in iPSC-derived differentiated cells such as neurons would be valuable for both therapy and gene discover, but has been a challenge because of the difficulty of transfecting postmitotic cells. Nonviral physical- or chemical-based methods such as electroporation, nucleofection, and lipofection are inefficient in transfecting postmitotic cells [26]. Viral vectors such as lentiviral and retroviral systems can transduce neurons with high efficiency, but are primarily used for stable genomic modification and transduction is associated with random integration of transgene. Here, we used an episomal baculoviral-based vector to achieve efficient expression of transgene in iPSC-derived NSCs and particularly in postmitotic neurons. This nonintegration method of high efficiency transfection in human neurons may enhance the utilization of iPSCs for disease modeling as it provides a powerful tool to study neuronal cell biology.
