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

McCullough KC, Milona P, Thomann-Harwood L, Démoulins T, Englezou P, Suter R, Ruggli N - Vaccines (Basel) (2014)

Bottom Line: 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.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 Article: PubMed Central - PubMed

Affiliation: Institute of Virology and Immunology, CH-3147 Mittelhaeusern, Switzerland. kenneth.mccullough@vetsuisse.unibe.ch.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Delivery of RepRNA to DCs by nanoparticulate delivery vehicles. The delivery vehicles can be composed of polysaccharides, lipids, lipoproteins or combinations thereof. The nature of the delivery vehicle composition is to provide encapsulation of the RepRNA to protect against RNases, facilitate delivery to DCs and ensure a level of compaction enabling the RepRNA to interact with the ribosomal translation machinery. The surface of the nanoparticulate delivery vehicle may be coated to enhance stability and/or provide a means of enhance targeting of the DCs.
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vaccines-02-00735-f001: Delivery of RepRNA to DCs by nanoparticulate delivery vehicles. The delivery vehicles can be composed of polysaccharides, lipids, lipoproteins or combinations thereof. The nature of the delivery vehicle composition is to provide encapsulation of the RepRNA to protect against RNases, facilitate delivery to DCs and ensure a level of compaction enabling the RepRNA to interact with the ribosomal translation machinery. The surface of the nanoparticulate delivery vehicle may be coated to enhance stability and/or provide a means of enhance targeting of the DCs.

Mentions: Dendritic Cells (DCs) play crucial roles in promoting and regulating immune responses, including adaptive immune defences. An important aspect is their capacity for handling antigens for delivery and presentation to the adaptive immune defence compartments [1]. Advances over the past two decades have expanded synthetic delivery of vaccine antigens, particularly when employing biocompatible, biodegradable nanoparticulate delivery vehicles (Figure 1). Nanoparticulate formulations have proven capacities for facilitating protein (drug or antigen) uptake by DCs. However, we recently demonstrated that the antigen cargo is an important component in terms of targeting cell receptors [2]. RNA does not possess this capacity. Moreover, delivery of antigen requires endosomal or protoeosomal processing, which would not guarantee survival of an RNA vaccine or its requisite delivery to the cellular translation machinery. Likewise, delivery of RNA for interference therapy (RNAi) cannot ensure efficient delivery of RNA for translation; the RNA for RNAi has particular requirements and intracellular targets distinct from those for RNA translation.


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

McCullough KC, Milona P, Thomann-Harwood L, Démoulins T, Englezou P, Suter R, Ruggli N - Vaccines (Basel) (2014)

Delivery of RepRNA to DCs by nanoparticulate delivery vehicles. The delivery vehicles can be composed of polysaccharides, lipids, lipoproteins or combinations thereof. The nature of the delivery vehicle composition is to provide encapsulation of the RepRNA to protect against RNases, facilitate delivery to DCs and ensure a level of compaction enabling the RepRNA to interact with the ribosomal translation machinery. The surface of the nanoparticulate delivery vehicle may be coated to enhance stability and/or provide a means of enhance targeting of the DCs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494254&req=5

vaccines-02-00735-f001: Delivery of RepRNA to DCs by nanoparticulate delivery vehicles. The delivery vehicles can be composed of polysaccharides, lipids, lipoproteins or combinations thereof. The nature of the delivery vehicle composition is to provide encapsulation of the RepRNA to protect against RNases, facilitate delivery to DCs and ensure a level of compaction enabling the RepRNA to interact with the ribosomal translation machinery. The surface of the nanoparticulate delivery vehicle may be coated to enhance stability and/or provide a means of enhance targeting of the DCs.
Mentions: Dendritic Cells (DCs) play crucial roles in promoting and regulating immune responses, including adaptive immune defences. An important aspect is their capacity for handling antigens for delivery and presentation to the adaptive immune defence compartments [1]. Advances over the past two decades have expanded synthetic delivery of vaccine antigens, particularly when employing biocompatible, biodegradable nanoparticulate delivery vehicles (Figure 1). Nanoparticulate formulations have proven capacities for facilitating protein (drug or antigen) uptake by DCs. However, we recently demonstrated that the antigen cargo is an important component in terms of targeting cell receptors [2]. RNA does not possess this capacity. Moreover, delivery of antigen requires endosomal or protoeosomal processing, which would not guarantee survival of an RNA vaccine or its requisite delivery to the cellular translation machinery. Likewise, delivery of RNA for interference therapy (RNAi) cannot ensure efficient delivery of RNA for translation; the RNA for RNAi has particular requirements and intracellular targets distinct from those for RNA translation.

Bottom Line: 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.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 Article: PubMed Central - PubMed

Affiliation: Institute of Virology and Immunology, CH-3147 Mittelhaeusern, Switzerland. kenneth.mccullough@vetsuisse.unibe.ch.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus