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Polymers for Improving the In Vivo Transduction Efficiency of AAV2 Vectors 英文参考文献
PolymersforImprovingtheInVivoTransduction
EfficiencyofAAV2Vectors
GillesMoulay1,SylvieBoutin1,CaroleMasurier1,DanielScherman2,AntoineKichler1,2*
1ResearchDepartment,Genethon,Evry,France,2UMR8151CNRS-U1022INSERM,Universite′ Rene′ Descartes,ChimieParistech,Paris,France
Abstract
Background:Adeno-associatedvirushasattractedgreatattentionasvehicleforbody-widegenedelivery.However,forthe
successful treatment of a disease such as Duchenne muscular dystrophy infusion of very large amounts of vectors is
required. This not only raises questions about the technical feasibility of the large scale production but also about the
overallsafetyoftheapproach.Onewaytoovercometheseproblemswouldbetofindstrategiesabletoincreasetheinvivo
efficiency.
Methodology:Here,weinvestigatedwhetherpolymerscanactasadjuvantstoincreasetheinvivoefficiencyofAAV2.Our
strategyconsistedinthepre-injectionofpolymersbeforeintravenousadministrationofmicewithAAV2encodingamurine
secreted alkaline phosphatase (mSeAP). The transgene expression, vector biodistribution and tissue transduction were
studiedbyquantificationofthemSeAPproteinandrealtimePCR.Theinjectionofpolyinosinicacidandpolylysineresulted
inanincreaseofplasmaticmSeAPof2-and12-fold,respectively.Interestingly,polyinosinicacidpre-injectionsignificantly
reducedtheneutralizingantibodytiterraisedagainstAAV2.
Conclusions: Our results show that the pre-injection of polymers can improve the overall transduction efficiency of
systemicallyadministeredAAV2andreducethehumoralresponseagainstthecapsidproteins.
Citation: Moulay G, Boutin S, Masurier C, Scherman D, Kichler A (2010) Polymers for Improving the In Vivo Transduction Efficiency of AAV2 Vectors. PLoS
ONE5(12):e15576.doi:10.1371/journal.pone.0015576
Editor:RafaelLinden,UniversidadeFederaldoRiodeJaneiro,Brazil
ReceivedAugust18,2010;AcceptedNovember16,2010;PublishedDecember28,2010
Copyright: ? 2010 Moulay et al. This is an open-access article distributed under the terms of the Creative Commons Attribution
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