Cellular Microvesicle Pathways Can Be Targeted to Transfer Genetic Information between Non-Immune Cells 英文参考文献.docVIP

CellularMicrovesiclePathwaysCanBeTargetedto TransferGeneticInformationbetweenNon-ImmuneCells AmyM.Skinner1,2,S.LeeO’Neill1,2,PeterKurre1,2,3 * 1Pape′FamilyPediatricResearchInstitute,OregonHealthScienceUniversity,Portland,Oregon,UnitedStatesofAmerica,2DepartmentsofPediatrics,OregonHealth ScienceUniversity,Portland,Oregon,UnitedStatesofAmerica,3CellDevelopmentalBiology,OregonHealthScienceUniversity,Portland,Oregon,UnitedStatesof America Abstract Eukaryotic cellcommunicationis basedon proteinsignalingcascadesthat requiredirect cell-cellapposition,orreceptor engagementbysecretedmolecules.Thetransmissionofgeneticinformationisthoughttobeuncommon,apartfromrecent reports of exosomal RNA transfer in immune and glioblastoma cells. We wished to examine if existing microvesicle pathways could be directly targeted for the horizontal transfer of RNA genomes in less specialized cell types. Using replication-deficientretrovirusvector,studieshereinconfirmthatarangeofcellsroutinelysequesterasmallpopulationof these RNA genomes in a non-canonical compartment, refractory to antibody neutralization and unaffected by specific pharmacological inhibition of pathways involved in conventional viral trafficking. Our experiments further reveal the cytoplasmiccolocalizationofvectorgenomeswithtetraspaninproteinsaswellasthePI-3-kinasesensitivetraffickingand subsequent transmission to 2u targets. Collectively, our results indicate a scalable process whereby cells route vector genomestomultivesicularbodies(MVB)forcytoplasmictraffickingandexosomalrelease.Ourfindingsimplythatcellscan servetodeliverrecombinantpayload,targetedforthestablegeneticmodificationof2utargetcells. Citation:SkinnerAM,O’NeillSL,KurreP(2009)CellularMicrovesiclePathwaysCanBeTargetedtoTransferGeneticInformationbetweenNon-ImmuneCells.PLoS ONE4(7):e6219.doi:10.1371/journal.pone.0006219 Editor:StefanWo¨lfl,Universita¨t Heidelberg,Germany ReceivedMarch12,2009;AcceptedJune17,2009;PublishedJuly13,2009 Copyright: ? 2009 Skinner et al.