Therapeutic Effects of Simultaneous Delivery of Nerve Growth Factor mRNA and Protein via Exosomes on Cerebral Ischemia
Stroke is the leading neurological cause of death and disability all over the world, with few effective drugs. Nerve growth factor (NGF) is well known for its multifaceted neuroprotective functions post-ischemia. However, the lack of an efficient approach to systemically deliver bioactive NGF into i...
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doaj-0b668e7aad9346f59816d118d4942f632020-11-25T03:05:55ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-09-0121512522Therapeutic Effects of Simultaneous Delivery of Nerve Growth Factor mRNA and Protein via Exosomes on Cerebral IschemiaJialei Yang0Shipo Wu1Lihua Hou2Danni Zhu3Shimin Yin4Guodong Yang5Yongjun Wang6China National Clinical Research Center for Neurological Diseases, Beijing 100070, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Department of Neurology, PLA Rocket Force Characteristic Medical Center, Beijing, China; Beijing Institute of Biotechnology, Beijing, ChinaBeijing Institute of Biotechnology, Beijing, ChinaBeijing Institute of Biotechnology, Beijing, ChinaBeijing Institute of Biotechnology, Beijing, ChinaDepartment of Neurology, PLA Rocket Force Characteristic Medical Center, Beijing, ChinaDepartment of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi’an, Shaanxi 710032, China; Corresponding author: Guodong Yang, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, No. 169 Changlexi Road, Xi’an, Shaanxi 710032, China.China National Clinical Research Center for Neurological Diseases, Beijing 100070, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Corresponding author: Yongjun Wang, China National Clinical Research Center for Neurological Diseases, Beijing, China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 Southwest of the Fourth Ring Road, Beijing 100070, China.Stroke is the leading neurological cause of death and disability all over the world, with few effective drugs. Nerve growth factor (NGF) is well known for its multifaceted neuroprotective functions post-ischemia. However, the lack of an efficient approach to systemically deliver bioactive NGF into ischemic region hinders its clinical application. In this study, we engineered the exosomes with RVG peptide on the surface for neuron targeting and loaded NGF into exosomes simultaneously, with the resultant exosomes denoted as NGF@ExoRVG. By systemic administration of NGF@ExoRVG, NGF was efficiently delivered into ischemic cortex, with a burst release of encapsulated NGF protein and de novo NGF protein translated from the delivered mRNA. Moreover, NGF@ExoRVG was found to be highly stable for preservation and function efficiently for a long time in vivo. Functional study revealed that the delivered NGF reduced inflammation by reshaping microglia polarization, promoted cell survival, and increased the population of doublecortin-positive cells, a marker of neuroblast. The results of our study suggest the potential therapeutic effects of NGF@ExoRVG for stroke. Moreover, the strategy proposed in our study may shed light on the clinical application of other neurotrophic factors for central nervous system diseases.http://www.sciencedirect.com/science/article/pii/S2162253120301748exosomesnerve growth factorischemiamRNA encapsulationtargeted deliverygene therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jialei Yang Shipo Wu Lihua Hou Danni Zhu Shimin Yin Guodong Yang Yongjun Wang |
spellingShingle |
Jialei Yang Shipo Wu Lihua Hou Danni Zhu Shimin Yin Guodong Yang Yongjun Wang Therapeutic Effects of Simultaneous Delivery of Nerve Growth Factor mRNA and Protein via Exosomes on Cerebral Ischemia Molecular Therapy: Nucleic Acids exosomes nerve growth factor ischemia mRNA encapsulation targeted delivery gene therapy |
author_facet |
Jialei Yang Shipo Wu Lihua Hou Danni Zhu Shimin Yin Guodong Yang Yongjun Wang |
author_sort |
Jialei Yang |
title |
Therapeutic Effects of Simultaneous Delivery of Nerve Growth Factor mRNA and Protein via Exosomes on Cerebral Ischemia |
title_short |
Therapeutic Effects of Simultaneous Delivery of Nerve Growth Factor mRNA and Protein via Exosomes on Cerebral Ischemia |
title_full |
Therapeutic Effects of Simultaneous Delivery of Nerve Growth Factor mRNA and Protein via Exosomes on Cerebral Ischemia |
title_fullStr |
Therapeutic Effects of Simultaneous Delivery of Nerve Growth Factor mRNA and Protein via Exosomes on Cerebral Ischemia |
title_full_unstemmed |
Therapeutic Effects of Simultaneous Delivery of Nerve Growth Factor mRNA and Protein via Exosomes on Cerebral Ischemia |
title_sort |
therapeutic effects of simultaneous delivery of nerve growth factor mrna and protein via exosomes on cerebral ischemia |
publisher |
Elsevier |
series |
Molecular Therapy: Nucleic Acids |
issn |
2162-2531 |
publishDate |
2020-09-01 |
description |
Stroke is the leading neurological cause of death and disability all over the world, with few effective drugs. Nerve growth factor (NGF) is well known for its multifaceted neuroprotective functions post-ischemia. However, the lack of an efficient approach to systemically deliver bioactive NGF into ischemic region hinders its clinical application. In this study, we engineered the exosomes with RVG peptide on the surface for neuron targeting and loaded NGF into exosomes simultaneously, with the resultant exosomes denoted as NGF@ExoRVG. By systemic administration of NGF@ExoRVG, NGF was efficiently delivered into ischemic cortex, with a burst release of encapsulated NGF protein and de novo NGF protein translated from the delivered mRNA. Moreover, NGF@ExoRVG was found to be highly stable for preservation and function efficiently for a long time in vivo. Functional study revealed that the delivered NGF reduced inflammation by reshaping microglia polarization, promoted cell survival, and increased the population of doublecortin-positive cells, a marker of neuroblast. The results of our study suggest the potential therapeutic effects of NGF@ExoRVG for stroke. Moreover, the strategy proposed in our study may shed light on the clinical application of other neurotrophic factors for central nervous system diseases. |
topic |
exosomes nerve growth factor ischemia mRNA encapsulation targeted delivery gene therapy |
url |
http://www.sciencedirect.com/science/article/pii/S2162253120301748 |
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