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

Soonbong Baek, Jaesur Oh, Juhyun Song, Hwan Choi, Junsang Yoo, Gui Yeon Park, Jin Han, Yujung Chang, Hanseul Park, Hongwon Kim, Ssang Goo Cho, Byung Soo Kim, Jongpil Kim

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

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.

Original languageEnglish
Article number1601993
JournalSmall
Volume13
Issue number5
DOIs
StatePublished - 3 Feb 2017

Keywords

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

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