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Vaccines 2014, 2(4), 735-754;

Self-Amplifying Replicon RNA Vaccine Delivery to Dendritic Cells by Synthetic Nanoparticles

Institute of Virology and Immunology, CH-3147 Mittelhaeusern, Switzerland
Author to whom correspondence should be addressed.
Microsynth AG, CH-9436 Balgach, Switzerland.
Received: 3 June 2014 / Revised: 29 August 2014 / Accepted: 28 September 2014 / Published: 16 October 2014
(This article belongs to the Special Issue Vaccine Vector)
PDF [499 KB, uploaded 16 October 2014]


Dendritic cells (DC) play essential roles determining efficacy of vaccine delivery with respect to immune defence development and regulation. This renders DCs important targets for vaccine delivery, particularly RNA vaccines. While delivery of interfering RNA oligonucleotides to the appropriate intracellular sites for RNA-interference has proven successful, the methodologies are identical for RNA vaccines, which require delivery to RNA translation sites. Delivery of mRNA has benefitted from application of cationic entities; these offer value following endocytosis of RNA, when cationic or amphipathic properties can promote endocytic vesicle membrane perturbation to facilitate cytosolic translocation. The present review presents how such advances are being applied to the delivery of a new form of RNA vaccine, replicons (RepRNA) carrying inserted foreign genes of interest encoding vaccine antigens. Approaches have been developed for delivery to DCs, leading to the translation of the RepRNA and encoded vaccine antigens both in vitro and in vivo. Potential mechanisms favouring efficient delivery leading to translation are discussed with respect to the DC endocytic machinery, showing the importance of cytosolic translocation from acidifying endocytic structures. The review relates the DC endocytic pathways to immune response induction, and the potential advantages for these self-replicating RNA vaccines in the near future. View Full-Text
Keywords: self-replicating replicon RNA; targeting dendritic cells; nanoparticle delivery self-replicating replicon RNA; targeting dendritic cells; nanoparticle delivery

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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McCullough, K.C.; Milona, P.; Thomann-Harwood, L.; Démoulins, T.; Englezou, P.; Suter, R.; Ruggli, N. Self-Amplifying Replicon RNA Vaccine Delivery to Dendritic Cells by Synthetic Nanoparticles. Vaccines 2014, 2, 735-754.

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