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Generation of Integration‐Free Induced Neurons Using Graphene Oxide‐Polyethylenimine
Author(s) -
Baek Soonbong,
Oh Jaesur,
Song Juhyun,
Choi Hwan,
Yoo Junsang,
Park GuiYeon,
Han Jin,
Chang Yujung,
Park Hanseul,
Kim Hongwon,
Cho SsangGoo,
Kim ByungSoo,
Kim Jongpil
Publication year - 2017
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201601993
Subject(s) - reprogramming , polyethylenimine , somatic cell , gene delivery , microbiology and biotechnology , transduction (biophysics) , transgene , biology , genetic enhancement , chemistry , cell , cell culture , gene , genetics , transfection , biochemistry
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.