Axonal-Transport-Mediated Gene Transduction in the Interior of Rat Bone 英文参考文献.docVIP

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Axonal-Transport-Mediated Gene Transduction in the Interior of Rat Bone 英文参考文献.doc

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Axonal-Transport-Mediated Gene Transduction in the Interior of Rat Bone 英文参考文献

Axonal-Transport-MediatedGeneTransductioninthe InteriorofRatBone ToshitakaOkabayashi1*,KuniakiNakanishi2,ToyokazuTsuchihara1,HiroshiArino1,YasuoYoshihara1, SusumuTominaga3,MakiUenoyama4,ShinyaSuzuki4,MasatakaAsagiri5,KoichiNemoto1 1Department of Orthopaedic Surgery, National Defense Medical College, Saitama, Japan, 2Department of Laboratory Medicine, National Defense Medical College Hospital,Saitama,Japan,3DepartmentofPathologyandLaboratoryMedicine,NationalDefenseMedicalCollege,Saitama,Japan,4DivisionofEnvironmentalMedicine, National Defense Medical College Research Institute, Saitama, Japan, 5Department of Chemistry and Biochemistry, University of California San Diego, San Diego, California,UnitedStatesofAmerica Abstract Background:Genetransductionhasbeenconsideredadvantageousforthesustaineddeliveryofproteinstospecifictarget tissues.However,inthecaseofhardtissues,suchasbone,localgenedeliveryremainsproblematicowingtoanatomical accessibilitylimitationsofthetargetsites. Methodology/PrincipalFindings:Here,weevaluatedthefeasibilityofexogenousgenetransductionintheinteriorofbone viaaxonaltransportfollowingintramuscularadministrationofanonviralvector.Ahighexpressionlevelofthetransduced genewasachievedinthetibiaipsilateraltotheinjectedtibialisanteriormuscle,aswellasintheipsilateralsciaticnerveand dorsalrootganglia.Insciatictransectionrats,thegeneexpressionlevelwassignificantlyloweredinbone. Conclusions/Significance: These results suggest that axonal transport is critical for gene transduction. Our study may provideabasisfordevelopingtherapeuticmethodsforefficientgenedeliveryintohardtissues. Citation: Okabayashi T, Nakanishi K, Tsuchihara T, Arino H, Yoshihara Y, et al. (2010) Axonal-Transport-Mediated Gene Transduction in the Interior of Rat Bone.PLoSONE5(9):e13034.doi:10.1371/journal.pone.0013034 Editor:AlfredLewin,UniversityofFlorida,UnitedStatesofAmerica ReceivedMay26,2010;AcceptedSeptember6,2010;PublishedSeptember28,2010 Copyright:?2010Okabayashietal.Thisisanopen-acce