Enhanced gene delivery in porcine vasculature tissue following incorporation of adeno-associated virus nanoparticles into porous silicon microparticles

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dc.citation.firstpage113en_US
dc.citation.journalTitleJournal of Controlled Releaseen_US
dc.citation.lastpage121en_US
dc.citation.volumeNumber194en_US
dc.contributor.authorMcConnell, Kellie I.en_US
dc.contributor.authorRhudy, Jessicaen_US
dc.contributor.authorYokoi, Kenjien_US
dc.contributor.authorGu, Jianhuaen_US
dc.contributor.authorMack, Aaronen_US
dc.contributor.authorSuh, Junghaeen_US
dc.contributor.authorLa Francesca, Saverioen_US
dc.contributor.authorSakamoto, Jasonen_US
dc.contributor.authorSerda, Rita E.en_US
dc.date.accessioned2015-12-18T19:57:39Zen_US
dc.date.available2015-12-18T19:57:39Zen_US
dc.date.issued2014en_US
dc.description.abstractThere is an unmet clinical need to increase lung transplant successes, patient satisfaction and to improve mortality rates. We offer the development of a nanovector-based solution that will reduce the incidence of lung ischemic reperfusion injury (IRI) leading to graft organ failure through the successful ex vivo treatment of the lung prior to transplantation. The innovation is in the integrated application of our novel porous silicon (pSi) microparticles carrying adeno-associated virus (AAV) nanoparticles, and the use of our ex vivo lung perfusion/ventilation system for the modulation of pro-inflammatory cytokines initiated by ischemic pulmonary conditions prior to organ transplant that often lead to complications. Gene delivery of anti-inflammatory agents to combat the inflammatory cascade may be a promising approach to prevent IRI following lung transplantation. The rationale for the device is that the microparticle will deliver a large payload of virus to cells and serve to protect the AAV from immune recognition. The microparticleﾖnanoparticle hybrid device was tested both in vitro on cell monolayers and ex vivo using either porcine venous tissue or a pig lung transplantation model, which recapitulates pulmonary IRI that occurs clinically post-transplantation. Remarkably, loading AAV vectors into pSi microparticles increases gene delivery to otherwise non-permissive endothelial cells.en_US
dc.identifier.citationMcConnell, Kellie I., Rhudy, Jessica, Yokoi, Kenji, et al.. "Enhanced gene delivery in porcine vasculature tissue following incorporation of adeno-associated virus nanoparticles into porous silicon microparticles." <i>Journal of Controlled Release,</i> 194, (2014) Elsevier: 113-121. http://dx.doi.org/10.1016/j.jconrel.2014.08.020.en_US
dc.identifier.doihttp://dx.doi.org/10.1016/j.jconrel.2014.08.020en_US
dc.identifier.urihttps://hdl.handle.net/1911/87475en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.en_US
dc.subject.keywordMesoporous siliconen_US
dc.subject.keywordAdeno-associated virusen_US
dc.subject.keywordinflammationen_US
dc.subject.keywordlungen_US
dc.subject.keywordEndotheliumen_US
dc.subject.keywordEx vivo perfusionen_US
dc.titleEnhanced gene delivery in porcine vasculature tissue following incorporation of adeno-associated virus nanoparticles into porous silicon microparticlesen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpost-printen_US
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