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Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles

Authors Rodríguez-Gascón A, del Pozo-Rodríguez A, Solinís MA

Received 18 December 2013

Accepted for publication 15 February 2014

Published 10 April 2014 Volume 2014:9(1) Pages 1833—1843

DOI https://doi.org/10.2147/IJN.S39810

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Alicia Rodríguez-Gascón, Ana del Pozo-Rodríguez, María Ángeles Solinís

Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain

Abstract: Self-amplifying RNA or RNA replicon is a form of nucleic acid-based vaccine derived from either positive-strand or negative-strand RNA viruses. The gene sequences encoding structural proteins in these RNA viruses are replaced by mRNA encoding antigens of interest as well as by RNA polymerase for replication and transcription. This kind of vaccine has been successfully assayed with many different antigens as vaccines candidates, and has been shown to be potent in several animal species, including mice, nonhuman primates, and humans. A key challenge to realizing the broad potential of self-amplifying vaccines is the need for safe and effective delivery methods. Ideally, an RNA nanocarrier should provide protection from blood nucleases and extended blood circulation, which ultimately would increase the possibility of reaching the target tissue. The delivery system must then be internalized by the target cell and, upon receptor-mediated endocytosis, must be able to escape from the endosomal compartment into the cell cytoplasm, where the RNA machinery is located, while avoiding degradation by lysosomal enzymes. Further, delivery systems for systemic administration ought to be well tolerated upon administration. They should be safe, enabling the multiadministration treatment modalities required for improved clinical outcomes and, from a developmental point of view, production of large batches with reproducible specifications is also desirable. In this review, the concept of self-amplifying RNA vaccines and the most promising lipid-based delivery systems are discussed.

Keywords: self-amplifying RNA vaccine, RNA replicon, liposomes, solid lipid nanoparticles, nucleic acid vaccines

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