Exosome mediated delivery of miR-124 promotes neurogenesis after ischemia

Followup needed to create a stroke protocol out of this. 

Exosome mediated delivery of miR-124 promotes neurogenesis after ischemia

Title:

Exosome mediated delivery of miR-124 promotes neurogenesis after ischemia

Running title:

Exosomal delivery of miR-124 promotes neurogenesis

Authors:

Jialei Yang

a,b,1

, Xiufen Zhang

b,1

, Xiangjie Chen

c

, Lei Wang

a

*

, Guodong

Yang

b

*

Authors affiliations:

a

Department of Neurology, New Era Stroke Care and Re

search Institute, The General

Hospital of the PLA Rocket Force, 16 Xinjiekouwai A

venue, Beijing 100088, China.

b

Department of Biochemistry and Molecular Biology, S

chool of Basic Medicine, The

Fourth Military Medical University, 169 Changlexi R

oad, Xi’an, Shaanxi 710032,

China.

c

Department of Mathematics, Southeast University, Na

njing 211189, China.

1

These authors contribute equally to the work.

*Correspondence should be addressed to Dr. Guodong

Yang (yanggd@fmmu.edu.cn.)

and Dr. Lei Wang (hellowanglei068@163.com)

*Corresponding author:

Dr. Guodong Yang

Department of Biochemistry and Molecular Biology, S

chool of Basic Medicine,

Fourth Military Medical University, 169 Chang Le Xi

Road, Xi’an, Shaanxi 710032,

China.

Tel: +86-29-84774516

Fax: +86-29-84774937

Email: yanggd@fmmu.edu.cn.

Dr. Lei Wang

Department of Neurology, New Era Stroke Care and Re

search Institute, The Second

Artillery General Hospital, Chinese People’s Libera

tion Army, 16 Xinjiekouwai

Avenue, Beijing 100088, China.

Tel:+86-10-66343682

Email: hellowanglei068@163.com

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.