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Mol Ther Nucleic Acids. 2017 Jun 16;7:278-287. doi: 10.1016/j.omtn.2017.04.010. Epub 2017 Apr 13.

Exosome Mediated Delivery of miR-124 Promotes Neurogenesis after Ischemia.

Author information

1
Department of Neurology, New Era Stroke Care and Research Institute, The General Hospital of the PLA Rocket Force, 16 Xinjiekouwai Avenue, Beijing 100088, China; The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, School of Basic Medicine, The Fourth Military Medical University, 169 Changlexi Road, Xi'an, Shaanxi 710032, China.
2
The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, School of Basic Medicine, The Fourth Military Medical University, 169 Changlexi Road, Xi'an, Shaanxi 710032, China.
3
Department of Mathematics, Southeast University, Nanjing 211189, China.
4
Department of Neurology, New Era Stroke Care and Research Institute, The General Hospital of the PLA Rocket Force, 16 Xinjiekouwai Avenue, Beijing 100088, China. Electronic address: hellowanglei068@163.com.
5
The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, School of Basic Medicine, The Fourth Military Medical University, 169 Changlexi Road, Xi'an, Shaanxi 710032, China. Electronic address: yanggd@fmmu.edu.cn.

Abstract

The intrinsic ability of neurogenesis after stroke has been proven weak, which results in insufficient repair of injury in the nerve system. Recent studies suggest multiple microRNAs (miRNAs) are involved in the neuroremodeling process. Targeted miRNAs delivery for amplification of neurogenesis is promising in promoting the prognosis after ischemia. Here, we showed that modified exosomes, with rabies virus glycoprotein (RVG) fused to exosomal protein lysosome-associated membrane glycoprotein 2b (Lamp2b), could efficiently deliver miR-124 to the infarct site. Systemic administration of RVG-exosomes loaded with miR-124 promoted cortical neural progenitors to obtain neuronal identity and protect against ischemic injury by robust cortical neurogenesis. Our study suggests that RVG-exosomes can be utilized therapeutically for the targeted delivery of gene drugs to the brain, thus having great potential for clinical applications.

KEYWORDS:

exosome; ischemia; miRNA; neurogenesis; targeted drug delivery

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