eprintid: 1482079 rev_number: 17 eprint_status: archive userid: 608 dir: disk0/01/48/20/79 datestamp: 2016-04-18 12:13:10 lastmod: 2019-02-18 04:36:48 status_changed: 2016-04-18 12:13:10 type: article metadata_visibility: show creators_name: Yilmazer, A creators_name: Tian, B creators_name: Kostarelos, K title: Development of Dual-Activity Vectors by Co-Envelopment of Adenovirus and SiRNA in Artificial Lipid Bilayers ispublished: pub divisions: A01 divisions: B02 divisions: C08 divisions: D10 divisions: G08 note: Copyright © 2014 Yilmazer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. abstract: 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. date: 2014-12-12 date_type: published official_url: http://dx.doi.org/10.1371/journal.pone.0114985 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 1124117 doi: 10.1371/journal.pone.0114985 lyricists_name: Kostarelos, Kostas lyricists_id: KKOST53 actors_name: Kostarelos, Kostas actors_name: Allington-Smith, Dominic actors_id: KKOST53 actors_id: DAALL44 actors_role: owner actors_role: impersonator full_text_status: public publication: PLOS One volume: 9 number: 12 article_number: e114985 issn: 1932-6203 editors_name: Hong, S-S citation: Yilmazer, A; Tian, B; Kostarelos, K; (2014) Development of Dual-Activity Vectors by Co-Envelopment of Adenovirus and SiRNA in Artificial Lipid Bilayers. PLOS One , 9 (12) , Article e114985. 10.1371/journal.pone.0114985 <https://doi.org/10.1371/journal.pone.0114985>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1482079/1/Development%20of%20Dual-Activity%20Vectors%20by%20Co-Envelopment%20of%20Adenovirus%20and%20SiRNA%20in%20Artificial%20Lipid%20Bilayers.PDF