Coatsome-replicon vehicles: Self-replicating RNA vaccines against infectious diseases.

Nanomedicine : nanotechnology, biology, and medicine 2023 Apr

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Herein, we provide the first description of a synthetic delivery method for self-replicating replicon RNAs (RepRNA) derived from classical swine fever virus (CSFV) using a Coatsome-replicon vehicle based on Coatsome® SS technologies. This results in an unprecedented efficacy when compared to well-established polyplexes, with up to ∼65 fold-increase of the synthesis of RepRNA-encoded gene of interest (GOI). We demonstrated the efficacy of such Coatsome-replicon vehicles for RepRNA-mediated induction of CD8 T-cell responses in mice. Moreover, we provide new insights on physical properties of the RepRNA, showing that the removal of all CSFV structural protein genes has a positive effect on the translation of the GOI. Finally, we successfully engineered RepRNA constructs encoding a porcine reproductive and respiratory syndrome virus (PRRSV) antigen, providing an example of antigen expression with potential application to combat viral diseases. The versatility and simplicity of modifying and manufacturing these Coatsome-replicon vehicle formulations represents a major asset to tackle foreseeable emerging pandemics. Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Thomas Démoulins, Kai Schulze, Thomas Ebensen, Navapon Techakriengkrai, Teerawut Nedumpun, Pavlos C Englezou, Markus Gerber, Ruslan Hlushchuk, Darien Toledo, Valentin Djonov, Stephan von Gunten, Kenneth C McCullough, Matthias Liniger, Carlos A Guzmán, Sanipa Suradhat, Nicolas Ruggli. Coatsome-replicon vehicles: Self-replicating RNA vaccines against infectious diseases. Nanomedicine : nanotechnology, biology, and medicine. 2023 Apr;49:102655