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Small. 2017 Feb;13(5). doi: 10.1002/smll.201601993. Epub 2016 Nov 7.

Generation of Integration-Free Induced Neurons Using Graphene Oxide-Polyethylenimine.

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Lab of Stem Cells and Cell Reprogramming, Department of Biomedical Engineering (BK21plus Team), Dongguk University, Seoul, 100-715, Republic of Korea.
School of Chemical and Biological Engineering, Seoul National University, Seoul, 151-742, Republic of Korea.
Department of Biomedical Sciences, Center for Creative Biomedical Scientists at Chonnam National University, Gwangju, 61469, Republic of Korea.
Department of Stem Cell and Regenerative Biology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Seoul, 05029, Republic of Korea.
Bio-MAX Institute, Institute of Chemical Processes, Seoul National University, Seoul, 151-742, Republic of Korea.


Direct conversion of somatic cells into induced neurons (iNs) without inducing pluripotency has great therapeutic potential for treating central nervous system diseases. Reprogramming of somatic cells to iNs requires the introduction of several factors that drive cell-fate conversion, and viruses are commonly used to deliver these factors into somatic cells. However, novel gene-delivery systems that do not integrate transgenes into the genome are required to generate iNs for safe human clinical applications. In this study, it is investigated whether graphene oxide-polyethylenimine (GO-PEI) complexes are an efficient and safe system for messenger RNA delivery for direct reprogramming of iNs. The GO-PEI complexes show low cytotoxicity, high delivery efficiency, and directly converted fibroblasts into iNs without integrating factors into the genome. Moreover, in vivo transduction of reprogramming factors into the brain with GO-PEI complexes facilitates the production of iNs that alleviated Parkinson's disease symptoms in a mouse model. Thus, the GO-PEI delivery system may be used to safely obtain iNs and could be used to develop direct cell reprogramming-based therapies for neurodegenerative diseases.


direct conversion; fibroblasts; gene delivery; graphene; mRNA; neuron; non-integration


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