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

作　　者：Jingzhou Liu Xin Xin Jiejie Sun Yueyue Fan Xun Zhou Wei Gong Meiyan Yang Zhiping Li Yuli Wang Yang Yang Chunsheng Gao 

机构地区：[1]State Key Laboratory of Toxicology and Medical Countermeasures,Beijing Institute of Pharmacology and Toxicology,Beijing,China [2]Academy of Medical Engineering and Translational Medicine,Medical College,Tianjin University,Tianjin,China

出　　处：《Neural Regeneration Research》2024年第3期629-635,共7页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.82073783(to YY);the Natural Science Foundation of Beijing,No.7212160(to YY).

摘　　要：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.

关 键 词：AAV9P1 ASTROCYTES astrocyte-to-neuron conversion GFAP promoter glial scar induced neurons neuronal reprogramming P1 peptide PTBP1 traumatic brain injury 

分 类 号：R651.15[医药卫生—外科学] R-332[医药卫生—临床医学]