Tropism-shifted AAV-PHP.eB-mediated bFGF gene therapy promotes varied neurorestoration after ischemic stroke in miceOA
AAV-PHP.eB is an artificial adeno-associated virus(AAV)that crosses the blood-brain barrier and targets neurons more efficiently than other AAVs when administered systematically.While AAV-PHP.eB has been used in various disease models,its cellular tropism in cerebrovascular diseases remains unclear.In the present study,we aimed to elucidate the tropism of AAV-PHP.eB for different cell types in the brain in a mouse model of ischemic stroke and evaluate its effectiveness in mediating basic fibroblast growth factor(bFGF)gene therapy.Mice were injected intravenously with AAV-PHP.eB either 14 days prior to(pre-stroke)or 1 day following(post-stroke)transient middle cerebral artery occlusion.Notably,we observed a shift in tropism from neurons to endothelial cells with post-stroke administration of AAV-PHP.eB-mNeonGreen(mNG).This endothelial cell tropism correlated strongly with expression of the endothelial membrane receptor lymphocyte antigen 6 family member A(Ly6A).Furthermore,AAV-PHP.eB-mediated overexpression of bFGF markedly improved neurobehavioral outcomes and promoted long-term neurogenesis and angiogenesis post-ischemic stroke.Our findings underscore the significance of considering potential tropism shifts when utilizing AAV-PHP.eB-mediated gene therapy in neurological diseases and suggest a promising new strategy for bFGF gene therapy in stroke treatment.
Rubing Shi;Jing Ye;Ze Liu;Cheng Wang;Shengju Wu;Hui Shen;Qian Suo;Wanlu Li;Xiaosong He;Zhijun Zhang;Yaohui Tang;Guo-Yuan Yang;Yongting Wang
Med-X Research Institute and School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai,ChinaMed-X Research Institute and School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai,ChinaMed-X Research Institute and School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai,ChinaMed-X Research Institute and School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai,ChinaMed-X Research Institute and School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai,ChinaMed-X Research Institute and School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai,ChinaMed-X Research Institute and School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai,ChinaMed-X Research Institute and School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai,ChinaDepartment of Emergency,the Second Affiliated Hospital,Department of Human Anatomy,School of Basic Science,Guangzhou Medical University,Guangzhou,Guangdong Province,ChinaMed-X Research Institute and School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai,ChinaMed-X Research Institute and School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai,ChinaMed-X Research Institute and School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai,ChinaMed-X Research Institute and School of Biomedical Engineering,Shanghai Jiao Tong University,Shanghai,China
医药卫生
AAV-PHP.eBangiogenesisbasic fibroblast growth factorgene therapyischemic strokeLy6Aneurogenesisneurological functiontransient middle cerebral artery occlusiontropism
《Neural Regeneration Research》 2026 (2)
P.704-714,11
supported by the National Natural Science Foundation of China,Nos.81870921(to YW),81974179(to ZZ),82271320(to ZZ),82071284(to YT)National Key R&D Program of China,No.2022YFA1603600(to ZZ),2019YFA0112000(to YT)Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY).
评论