Yang Jialei, Zhang Xiufen, Chen Xiangjie, Wang Lei, Yang Guodong
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.
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.
Mol Ther Nucleic Acids. 2017 Jun 16;7:278-287. doi: 10.1016/j.omtn.2017.04.010. Epub 2017 Apr 13.
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.
中风后神经发生的内在能力已被证明较弱,这导致神经系统损伤的修复不足。最近的研究表明,多种微小RNA(miRNA)参与了神经重塑过程。靶向递送miRNA以增强神经发生在促进缺血后的预后方面具有前景。在此,我们表明,将狂犬病毒糖蛋白(RVG)与外泌体蛋白溶酶体相关膜糖蛋白2b(Lamp2b)融合的修饰外泌体能够有效地将miR-124递送至梗死部位。全身给予负载miR-124的RVG-外泌体可促进皮质神经祖细胞获得神经元特性,并通过强大的皮质神经发生来预防缺血性损伤。我们的研究表明,RVG-外泌体可用于将基因药物靶向递送至大脑进行治疗,因此具有巨大的临床应用潜力。