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Nuclear localization signals in phage terminal proteins provide a novel gene delivery tool in mammalian cells
Terminal proteins (TPs) of bacteriophages prime DNA replication and become covalently linked to the genome ends. Unexpectedly, we have found functional eukaryotic nuclear localization signals (NLSs) within the TP sequences of bacteriophages from diverse families and hosts. Given the role of bacterio...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Landes Bioscience
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609834/ https://www.ncbi.nlm.nih.gov/pubmed/23750294 http://dx.doi.org/10.4161/cib.22829 |
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author | Redrejo-Rodríguez, Modesto Muñoz-Espín, Daniel Holguera, Isabel Mencía, Mario Salas, Margarita |
author_facet | Redrejo-Rodríguez, Modesto Muñoz-Espín, Daniel Holguera, Isabel Mencía, Mario Salas, Margarita |
author_sort | Redrejo-Rodríguez, Modesto |
collection | PubMed |
description | Terminal proteins (TPs) of bacteriophages prime DNA replication and become covalently linked to the genome ends. Unexpectedly, we have found functional eukaryotic nuclear localization signals (NLSs) within the TP sequences of bacteriophages from diverse families and hosts. Given the role of bacteriophages as vehicles for horizontal gene transfer (HGT), we postulated that viral genomes that have covalently linked NLS-containing terminal proteins might behave as vectors for HGT between bacteria and the eukaryotic nucleus. To validate this hypothesis, we profited from the in vitro Φ29 amplification system that allows the amplification of heterologous DNAs producing linear molecules of DNA with TP covalently attached to both 5' ends. Interestingly, these in vitro-generated TP-DNA molecules showed enhanced gene delivery in mammalian cells, supporting a possible role in HGT by transferring genes between prokaryotes and eukaryotes. Moreover, these TP-DNA molecules are a useful tool to amplify and subsequently deliver genes efficiently into the eukaryotic nucleus. Here, we suggest various possible applications and further developments of the technique with biotechnological and therapeutic purposes. |
format | Online Article Text |
id | pubmed-3609834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Landes Bioscience |
record_format | MEDLINE/PubMed |
spelling | pubmed-36098342013-06-07 Nuclear localization signals in phage terminal proteins provide a novel gene delivery tool in mammalian cells Redrejo-Rodríguez, Modesto Muñoz-Espín, Daniel Holguera, Isabel Mencía, Mario Salas, Margarita Commun Integr Biol Article Addendum Terminal proteins (TPs) of bacteriophages prime DNA replication and become covalently linked to the genome ends. Unexpectedly, we have found functional eukaryotic nuclear localization signals (NLSs) within the TP sequences of bacteriophages from diverse families and hosts. Given the role of bacteriophages as vehicles for horizontal gene transfer (HGT), we postulated that viral genomes that have covalently linked NLS-containing terminal proteins might behave as vectors for HGT between bacteria and the eukaryotic nucleus. To validate this hypothesis, we profited from the in vitro Φ29 amplification system that allows the amplification of heterologous DNAs producing linear molecules of DNA with TP covalently attached to both 5' ends. Interestingly, these in vitro-generated TP-DNA molecules showed enhanced gene delivery in mammalian cells, supporting a possible role in HGT by transferring genes between prokaryotes and eukaryotes. Moreover, these TP-DNA molecules are a useful tool to amplify and subsequently deliver genes efficiently into the eukaryotic nucleus. Here, we suggest various possible applications and further developments of the technique with biotechnological and therapeutic purposes. Landes Bioscience 2013-03-01 2013-03-01 /pmc/articles/PMC3609834/ /pubmed/23750294 http://dx.doi.org/10.4161/cib.22829 Text en Copyright © 2013 Landes Bioscience http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. |
spellingShingle | Article Addendum Redrejo-Rodríguez, Modesto Muñoz-Espín, Daniel Holguera, Isabel Mencía, Mario Salas, Margarita Nuclear localization signals in phage terminal proteins provide a novel gene delivery tool in mammalian cells |
title | Nuclear localization signals in phage terminal proteins provide a novel gene delivery tool in mammalian cells |
title_full | Nuclear localization signals in phage terminal proteins provide a novel gene delivery tool in mammalian cells |
title_fullStr | Nuclear localization signals in phage terminal proteins provide a novel gene delivery tool in mammalian cells |
title_full_unstemmed | Nuclear localization signals in phage terminal proteins provide a novel gene delivery tool in mammalian cells |
title_short | Nuclear localization signals in phage terminal proteins provide a novel gene delivery tool in mammalian cells |
title_sort | nuclear localization signals in phage terminal proteins provide a novel gene delivery tool in mammalian cells |
topic | Article Addendum |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609834/ https://www.ncbi.nlm.nih.gov/pubmed/23750294 http://dx.doi.org/10.4161/cib.22829 |
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