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Development of Dual-Activity Vectors by Co-Envelopment of Adenovirus and SiRNA in Artificial Lipid Bilayers
Gene therapy with human adenovirus type 5 (Ad5) has been extensively explored for the treatment of diseases resistant to traditional therapies. Intravenous administration leads to rapid clearance from blood circulation and high liver accumulation, which restrict the use of Ad-based vectors in clinic...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264847/ https://www.ncbi.nlm.nih.gov/pubmed/25501573 http://dx.doi.org/10.1371/journal.pone.0114985 |
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author | Yilmazer, Açelya Tian, Bowen Kostarelos, Kostas |
author_facet | Yilmazer, Açelya Tian, Bowen Kostarelos, Kostas |
author_sort | Yilmazer, Açelya |
collection | PubMed |
description | Gene therapy with human adenovirus type 5 (Ad5) has been extensively explored for the treatment of diseases resistant to traditional therapies. Intravenous administration leads to rapid clearance from blood circulation and high liver accumulation, which restrict the use of Ad-based vectors in clinical gene therapy protocols that involve systemic administration. We have previously proposed that such limitations can be improved by engineering artificial lipid envelopes around Ad and designed a variety of artificial lipid bilayer envelopes around the viral capsid. In this study, we sought to explore further opportunities that the artificially enveloped virus constructs could offer, by designing a previously unreported gene therapy vector by simultaneous envelopment of Ad and siRNA within the same lipid bilayer. Such a dual-activity vector can offer efficacious therapy for different genetic disorders where both turning on and switching off genes would be needed. Dynamic light scattering, transmission electron microscopy and atomic force microscopy were used to characterize these vectors. Agarose gel electrophoresis, Ribo green and dot blot assays showed that siRNA and Ad virions can be enveloped together within lipid bilayers at high envelopment efficiency. Cellular uptake and in vitro transfection experiments were carried out to show the feasibility of combining siRNA-mediated gene silencing with viral gene transfer using these newly designed dual-activity vectors. |
format | Online Article Text |
id | pubmed-4264847 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42648472014-12-19 Development of Dual-Activity Vectors by Co-Envelopment of Adenovirus and SiRNA in Artificial Lipid Bilayers Yilmazer, Açelya Tian, Bowen Kostarelos, Kostas PLoS One Research Article Gene therapy with human adenovirus type 5 (Ad5) has been extensively explored for the treatment of diseases resistant to traditional therapies. Intravenous administration leads to rapid clearance from blood circulation and high liver accumulation, which restrict the use of Ad-based vectors in clinical gene therapy protocols that involve systemic administration. We have previously proposed that such limitations can be improved by engineering artificial lipid envelopes around Ad and designed a variety of artificial lipid bilayer envelopes around the viral capsid. In this study, we sought to explore further opportunities that the artificially enveloped virus constructs could offer, by designing a previously unreported gene therapy vector by simultaneous envelopment of Ad and siRNA within the same lipid bilayer. Such a dual-activity vector can offer efficacious therapy for different genetic disorders where both turning on and switching off genes would be needed. Dynamic light scattering, transmission electron microscopy and atomic force microscopy were used to characterize these vectors. Agarose gel electrophoresis, Ribo green and dot blot assays showed that siRNA and Ad virions can be enveloped together within lipid bilayers at high envelopment efficiency. Cellular uptake and in vitro transfection experiments were carried out to show the feasibility of combining siRNA-mediated gene silencing with viral gene transfer using these newly designed dual-activity vectors. Public Library of Science 2014-12-12 /pmc/articles/PMC4264847/ /pubmed/25501573 http://dx.doi.org/10.1371/journal.pone.0114985 Text en © 2014 Yilmazer et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Yilmazer, Açelya Tian, Bowen Kostarelos, Kostas Development of Dual-Activity Vectors by Co-Envelopment of Adenovirus and SiRNA in Artificial Lipid Bilayers |
title | Development of Dual-Activity Vectors by Co-Envelopment of Adenovirus and SiRNA in Artificial Lipid Bilayers |
title_full | Development of Dual-Activity Vectors by Co-Envelopment of Adenovirus and SiRNA in Artificial Lipid Bilayers |
title_fullStr | Development of Dual-Activity Vectors by Co-Envelopment of Adenovirus and SiRNA in Artificial Lipid Bilayers |
title_full_unstemmed | Development of Dual-Activity Vectors by Co-Envelopment of Adenovirus and SiRNA in Artificial Lipid Bilayers |
title_short | Development of Dual-Activity Vectors by Co-Envelopment of Adenovirus and SiRNA in Artificial Lipid Bilayers |
title_sort | development of dual-activity vectors by co-envelopment of adenovirus and sirna in artificial lipid bilayers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264847/ https://www.ncbi.nlm.nih.gov/pubmed/25501573 http://dx.doi.org/10.1371/journal.pone.0114985 |
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