Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury

[INLINE:1] Traumatic brain injury results in neuronal loss and glial scar formation. Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury. Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue...

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Main Authors: Jingzhou Liu, Xin Xin, Jiejie Sun, Yueyue Fan, Xun Zhou, Wei Gong, Meiyan Yang, Zhiping Li, Yuli Wang, Yang Yang, Chunsheng Gao
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2024-01-01
Series:Neural Regeneration Research
Subjects:
Online Access:http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=3;spage=629;epage=635;aulast=Liu
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author Jingzhou Liu
Xin Xin
Jiejie Sun
Yueyue Fan
Xun Zhou
Wei Gong
Meiyan Yang
Zhiping Li
Yuli Wang
Yang Yang
Chunsheng Gao
author_facet Jingzhou Liu
Xin Xin
Jiejie Sun
Yueyue Fan
Xun Zhou
Wei Gong
Meiyan Yang
Zhiping Li
Yuli Wang
Yang Yang
Chunsheng Gao
author_sort Jingzhou Liu
collection DOAJ
description [INLINE:1] Traumatic brain injury results in neuronal loss and glial scar formation. Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury. Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue. However, previous studies have reported inconsistent results. In this study, an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects. The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes. Moreover, neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury. In summary, this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.
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spelling doaj.art-74c127c88ca04d55866119e84b5e90fc2023-10-30T11:47:16ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742024-01-0119362963510.4103/1673-5374.380907Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injuryJingzhou LiuXin XinJiejie SunYueyue FanXun ZhouWei GongMeiyan YangZhiping LiYuli WangYang YangChunsheng Gao[INLINE:1] Traumatic brain injury results in neuronal loss and glial scar formation. Replenishing neurons and eliminating the consequences of glial scar formation are essential for treating traumatic brain injury. Neuronal reprogramming is a promising strategy to convert glial scars to neural tissue. However, previous studies have reported inconsistent results. In this study, an AAV9P1 vector incorporating an astrocyte-targeting P1 peptide and glial fibrillary acidic protein promoter was used to achieve dual-targeting of astrocytes and the glial scar while minimizing off-target effects. The results demonstrate that AAV9P1 provides high selectivity of astrocytes and reactive astrocytes. Moreover, neuronal reprogramming was induced by downregulating the polypyrimidine tract-binding protein 1 gene via systemic administration of AAV9P1 in a mouse model of traumatic brain injury. In summary, this approach provides an improved gene delivery vehicle to study neuronal programming and evidence of its applications for traumatic brain injury.http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=3;spage=629;epage=635;aulast=Liuaav9p1; astrocytes; astrocyte-to-neuron conversion; gfap promoter; glial scar; induced neurons; neuronal reprogramming; p1 peptide; ptbp1; traumatic brain injury
spellingShingle Jingzhou Liu
Xin Xin
Jiejie Sun
Yueyue Fan
Xun Zhou
Wei Gong
Meiyan Yang
Zhiping Li
Yuli Wang
Yang Yang
Chunsheng Gao
Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury
Neural Regeneration Research
aav9p1; astrocytes; astrocyte-to-neuron conversion; gfap promoter; glial scar; induced neurons; neuronal reprogramming; p1 peptide; ptbp1; traumatic brain injury
title Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury
title_full Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury
title_fullStr Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury
title_full_unstemmed Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury
title_short Dual-targeting AAV9P1-mediated neuronal reprogramming in a mouse model of traumatic brain injury
title_sort dual targeting aav9p1 mediated neuronal reprogramming in a mouse model of traumatic brain injury
topic aav9p1; astrocytes; astrocyte-to-neuron conversion; gfap promoter; glial scar; induced neurons; neuronal reprogramming; p1 peptide; ptbp1; traumatic brain injury
url http://www.nrronline.org/article.asp?issn=1673-5374;year=2024;volume=19;issue=3;spage=629;epage=635;aulast=Liu
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