6533b86ffe1ef96bd12ce779
RESEARCH PRODUCT
Selective uptake of naked vaccine RNA by dendritic cells is driven by macropinocytosis and abrogated upon DC maturation.
Ugur SahinSebastian KreiterCedrik M. BrittenÖZlem TüreciMustafa DikenChristoph HuberAbderraouf Selmisubject
media_common.quotation_subjectGenetic enhancementCellular differentiationGene deliveryBiologyVirusMiceGeneticsAnimalsInternalizationMolecular Biologymedia_commonMice Inbred BALB CGene Transfer TechniquesRNACell DifferentiationDendritic cellDendritic CellsVirologyIn vitroCell biologyMice Inbred C57BLMolecular MedicinePinocytosisRNALymph Nodesdescription
Even though it is known for more than one decade that antigen-encoding RNA can deliver antigenic information to induce antigen-specific immunity against cancer, the nature and mechanism of RNA uptake have remained enigmatic. In this study, we investigated the pharmacokinetics of naked RNA administered into the lymph node. We observed that RNA is rapidly and selectively uptaken by lymph node dendritic cells (DCs). Furthermore, in vitro and in vivo studies revealed that the efficient internalization of RNA by human and murine DCs is primarily driven by macropinocytosis. Selective inhibition of macropinocytosis by compounds or as a consequence of DC maturation abrogated RNA internalization and delivery of encoded antigens. Our findings imply that bioavailability of recombinant RNA vaccines in vivo highly depends on the density and the maturation stage of DCs at the administration site and are of importance for the design of RNA-based clinical immunotherapy protocols.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-03-03 | Gene therapy |