Anti-amyloid beta single-chain Fv ameliorates behavioral impairment in Alzheimer's disease mice via adeno-associated virus delivery

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.