Details

Autor(en) / Beteiligte

• Démoulins, Thomas, PhD
• Milona, Panagiota, PhD
• Englezou, Pavlos C., PhD
• Ebensen, Thomas, PhD
• Schulze, Kai, PhD
• Suter, Rolf, PhD
• Pichon, Chantal, PhD
• Midoux, Patrick, PhD
• Guzmán, Carlos A., MD, PhD
• Ruggli, Nicolas, PhD
• McCullough, Kenneth C., PhD

Titel

Polyethylenimine-based polyplex delivery of self-replicating RNA vaccines

Ist Teil von

• Nanomedicine, 2016-04, Vol.12 (3), p.711-722

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract Self-amplifying replicon RNA (RepRNA) are large molecules (12-14 kb); their self-replication amplifies mRNA template numbers, affording several rounds of antigen production, effectively increasing vaccine antigen payloads. Their sensitivity to RNase-sensitivity and inefficient uptake by dendritic cells (DCs) – absolute requirements for vaccine design – were tackled by condensing RepRNA into synthetic, nanoparticulate, polyethylenimine (PEI)-polyplex delivery vehicles. Polyplex-delivery formulations for small RNA molecules cannot be transferred to RepRNA due to its greater size and complexity; the N:P charge ratio and impact of RepRNA folding would influence polyplex condensation, post-delivery decompaction and the cytosolic release essential for RepRNA translation. Polyplex-formulations proved successful for delivery of RepRNA encoding influenza virus hemagglutinin and nucleocapsid to DCs. Cytosolic translocation was facilitated, leading to RepRNA translation. This efficacy was confirmed in vivo , inducing both humoral and cellular immune responses. Accordingly, this paper describes the first PEI-polyplexes providing efficient delivery of the complex and large, self-amplifying RepRNA vaccines.