AAV介导AB单链抗体改善阿尔茨海默病模型小鼠行为受损 |
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作者姓名: | 蔡炯 钟彦伟 李方 王世真 |
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作者单位: | 中国医学科学院北京协和医院核医学科,解放军302医院传染病研究所病毒性肝炎研究室,中国医学科学院北京协和医院核医学科,中国医学科学院北京协和医院核医学科 |
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基金项目: | 国家自然科学基金项目(面上项目,重点项目,重大项目) |
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摘 要: | Intracranial delivery of human Fc-deleted antibody specific to amyloid-βpeptide(Aβ,anti-Aβ single-chain Fv,scFv)via adeno-associated virus(AAV)inhibits amyloid deposition in transgenic mice.However,the effects of AAV-mediated Fc-deleted antibody on animal behavior remain unclear.In this study,the anti-AβscFv antibody gene,isolated from phage display,was fused to the 5’end of the scFv antibody gene for antibody secretion by 2 rounds of polymerase chain reaction amplification.The fused antibody cDNA was cloned into a pSNAV2 plasmid under the control of the cytomegalovirus promoter.The sequence verified expression vector pSNAV2/scFv was transferred to BHK-21 cells,and stable transfected BHK-21/scFv cells were established by G418 selection and infected with the recombinant herpes simplex virus rHSV/repcap for AAV production.Recombinant AAV was injected into the left quadriceps femoris of PDAPP transgenic mice.After 3 months,Morris water-maze results confirmed significantly improved cognitive function in a mouse model of Alzheimer’s disease.
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关 键 词: | Alzheimer’s disease adeno-associated virus amyloid-β peptide single-chain antibody neurodegenerative diseases neural regeneration |
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