Intracellular nucleic acid delivery by the supercharged dengue virus capsid protein

Detalhes bibliográficos
Autor(a) principal: Freire, João Miguel
Data de Publicação: 2013
Outros Autores: Veiga, Ana Salomé, Conceição, Thaís M., Kowalczyk, Wioleta, Mohana-Borges, Ronaldo, Andreu, David, Santos, Nuno C., Poian, Andrea T. da, Castanho, Miguel A. R. B.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/10722
Resumo: © 2013 Freire et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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spelling Intracellular nucleic acid delivery by the supercharged dengue virus capsid protein© 2013 Freire et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Supercharged proteins are a recently identified class of proteins that have the ability to efficiently deliver functional macromolecules into mammalian cells. They were first developed as bioengineering products, but were later found in the human proteome. In this work, we show that this class of proteins with unusually high net positive charge is frequently found among viral structural proteins, more specifically among capsid proteins. In particular, the capsid proteins of viruses from the Flaviviridae family have all a very high net charge to molecular weight ratio (> +1.07/kDa), thus qualifying as supercharged proteins. This ubiquity raises the hypothesis that supercharged viral capsid proteins may have biological roles that arise from an intrinsic ability to penetrate cells. Dengue virus capsid protein was selected for a detailed experimental analysis. We showed that this protein is able to deliver functional nucleic acids into mammalian cells. The same result was obtained with two isolated domains of this protein, one of them being able to translocate lipid bilayers independently of endocytic routes. Nucleic acids such as siRNA and plasmids were delivered fully functional into cells. The results raise the possibility that the ability to penetrate cells is part of the native biological functions of some viral capsid proteins.This work was supported by Fundação para a Ciência e Tecnologia – Ministério da Educação e Ciência (FCT-MEC, Portugal) [PTDC/QUI-BIQ/112929/2009], by the European Union [projects FP7-PEOPLE IRSES (MEMPEPACROSS) and FP7-HEALTH-F3-2008-223414 (LEISHDRUG)], by the Spanish Ministry of Economy and Competitiveness (SAF2011-24899), the Generalitat de Catalunya (2009 SGR 492), by the Brazilian Conselho Nacional de Desenvolvimento Científico e Tecnoloógico (CNPq), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), and the National Institute of Science and Technology in Dengue (INCT-Dengue). JMF also acknowledges FCT-MEC for Ph.D. fellowship SFRH/BD/70423/2010.PLOS - Public Library of ScienceRepositório da Universidade de LisboaFreire, João MiguelVeiga, Ana SaloméConceição, Thaís M.Kowalczyk, WioletaMohana-Borges, RonaldoAndreu, DavidSantos, Nuno C.Poian, Andrea T. daCastanho, Miguel A. R. B.2014-03-11T12:12:17Z20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/10722engPLOS One December 2013, Volume 8, Issue 12, e814501932-6203http://dx.doi.org/10.1371/journal.pone.0081450info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T15:56:24Zoai:repositorio.ul.pt:10451/10722Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:34:39.228882Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Intracellular nucleic acid delivery by the supercharged dengue virus capsid protein
title Intracellular nucleic acid delivery by the supercharged dengue virus capsid protein
spellingShingle Intracellular nucleic acid delivery by the supercharged dengue virus capsid protein
Freire, João Miguel
title_short Intracellular nucleic acid delivery by the supercharged dengue virus capsid protein
title_full Intracellular nucleic acid delivery by the supercharged dengue virus capsid protein
title_fullStr Intracellular nucleic acid delivery by the supercharged dengue virus capsid protein
title_full_unstemmed Intracellular nucleic acid delivery by the supercharged dengue virus capsid protein
title_sort Intracellular nucleic acid delivery by the supercharged dengue virus capsid protein
author Freire, João Miguel
author_facet Freire, João Miguel
Veiga, Ana Salomé
Conceição, Thaís M.
Kowalczyk, Wioleta
Mohana-Borges, Ronaldo
Andreu, David
Santos, Nuno C.
Poian, Andrea T. da
Castanho, Miguel A. R. B.
author_role author
author2 Veiga, Ana Salomé
Conceição, Thaís M.
Kowalczyk, Wioleta
Mohana-Borges, Ronaldo
Andreu, David
Santos, Nuno C.
Poian, Andrea T. da
Castanho, Miguel A. R. B.
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Freire, João Miguel
Veiga, Ana Salomé
Conceição, Thaís M.
Kowalczyk, Wioleta
Mohana-Borges, Ronaldo
Andreu, David
Santos, Nuno C.
Poian, Andrea T. da
Castanho, Miguel A. R. B.
description © 2013 Freire et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-01-01T00:00:00Z
2014-03-11T12:12:17Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/10722
url http://hdl.handle.net/10451/10722
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PLOS One December 2013, Volume 8, Issue 12, e81450
1932-6203
http://dx.doi.org/10.1371/journal.pone.0081450
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eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv PLOS - Public Library of Science
publisher.none.fl_str_mv PLOS - Public Library of Science
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