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

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dc.citation.firstpage113
dc.citation.journalTitleJournal of Controlled Release
dc.citation.lastpage121
dc.citation.volumeNumber194
dc.contributor.authorMcConnell, Kellie I.
dc.contributor.authorRhudy, Jessica
dc.contributor.authorYokoi, Kenji
dc.contributor.authorGu, Jianhua
dc.contributor.authorMack, Aaron
dc.contributor.authorSuh, Junghae
dc.contributor.authorLa Francesca, Saverio
dc.contributor.authorSakamoto, Jason
dc.contributor.authorSerda, Rita E.
dc.date.accessioned2015-12-18T19:57:39Z
dc.date.available2015-12-18T19:57:39Z
dc.date.issued2014
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.
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.
dc.identifier.doihttp://dx.doi.org/10.1016/j.jconrel.2014.08.020
dc.identifier.urihttps://hdl.handle.net/1911/87475
dc.language.isoeng
dc.publisherElsevier
dc.rightsThis is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.
dc.subject.keywordMesoporous silicon
dc.subject.keywordAdeno-associated virus
dc.subject.keywordinflammation
dc.subject.keywordlung
dc.subject.keywordEndothelium
dc.subject.keywordEx vivo perfusion
dc.titleEnhanced gene delivery in porcine vasculature tissue following incorporation of adeno-associated virus nanoparticles into porous silicon microparticles
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpost-print
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