文献名：directgenetransfertotherespiratorytractofmicewithpureplasmidandlipid-formulateddna
作者：michaelj.mccluskie,1,2yongliangchu,5jiu-linxia,5joeljessee,5gulilatgebyehu,5andheatherl.davis1,2,3,4
1loebresearchinstitute,ottawa,canada.
2departmentofcellularandmolecularmedicine,
3departmentofmicrobiologyandimmunology,facultyofmedicine,
4schoolofrehabilitationsciences,facultyofhealthsciences,universityofottawa,ottawa,canada.
5lifetechnologies,inc.,rockville,md20850.
摘要：directgenetransferintotherespiratorysystemcouldbecarriedoutforeithertherapeuticorimmunizationpurposes.herewedemonstratethatcellsinthelungcantakeupandexpressplasmiddnaencodingaluciferasereportergenewhetheritisadministeredinnakedformorformulatedwithcationicliposomes.dependingonthelipidused,thetransfectionefficiencywithliposome-formulateddnamaybehigher,thesameas,orlessthanthatwithpureplasmiddna.tetramethyltetraalkylspermineanalogswithalkylgroupsof16or18carbonsanddmrie/cholesterolformulationsprovedparticularlyeffective.similarresultsforreportergeneexpressioninthelungwereobtainedwhetherthedna(nakedorlipidformulated)wasadministeredbyindirect,noninvasiveintranasaldelivery(inhaledorinstilled)orbyinvasive,directintratrachealdelivery(injectedorviaacannula).reportergeneexpressionpeaksaround4days,thenfallsoffdramaticallyby9days.thedose-responseislinear,atleastupto100μgplasmiddna,suggestingbettertransfectionefficienciesmightberealizediftherewasnotavolumelimitation.foragivendoseofdna,thebestresultsareobtainedwhenthednaismixedwiththeminimumamountoflipidthatcancomplexitcompley.theseresultsarediscussedinthecontextofdirectgenetransferforeithergenetherapyordeliveryofamucosaldnavaccine.