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

Alicia Rodríguez-Gascón, Ana del Pozo-Rodríguez, María Ángeles SolinísPharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of...

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Autores principales:	Rodríguez-Gascón A, del Pozo-Rodríguez A, Solinís MA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/cdedf95e144a4b0fa591a86673911f5f
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spelling	oai:doaj.org-article:cdedf95e144a4b0fa591a86673911f5f2021-12-02T02:35:13ZDevelopment of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles1178-2013https://doaj.org/article/cdedf95e144a4b0fa591a86673911f5f2014-04-01T00:00:00Zhttp://www.dovepress.com/development-of-nucleic-acid-vaccines-use-of-self-amplifying-rna-in-lip-a16423https://doaj.org/toc/1178-2013 Alicia Rodríguez-Gascón, Ana del Pozo-Rodríguez, María Ángeles SolinísPharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, SpainAbstract: 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 vaccinesRodríguez-Gascón Adel Pozo-Rodríguez ASolinís MADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 1833-1843 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Rodríguez-Gascón A del Pozo-Rodríguez A Solinís MA Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles
description	Alicia Rodríguez-Gascón, Ana del Pozo-Rodríguez, María Ángeles SolinísPharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Faculty of Pharmacy, Centro de Investigación Lascaray Ikergunea, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, SpainAbstract: 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
format	article
author	Rodríguez-Gascón A del Pozo-Rodríguez A Solinís MA
author_facet	Rodríguez-Gascón A del Pozo-Rodríguez A Solinís MA
author_sort	Rodríguez-Gascón A
title	Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles
title_short	Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles
title_full	Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles
title_fullStr	Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles
title_full_unstemmed	Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles
title_sort	development of nucleic acid vaccines: use of self-amplifying rna in lipid nanoparticles
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/cdedf95e144a4b0fa591a86673911f5f
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Development of nucleic acid vaccines: use of self-amplifying RNA in lipid nanoparticles

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