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

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    Author
    McConnell, Kellie I.; Rhudy, Jessica; Yokoi, Kenji; Gu, Jianhua; Mack, Aaron; More... Suh, Junghae; La Francesca, Saverio; Sakamoto, Jason; Serda, Rita E. Less...
    Date
    2014
    Abstract
    There 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.
    Citation
    McConnell, 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." Journal of Controlled Release, 194, (2014) Elsevier: 113-121. http://dx.doi.org/10.1016/j.jconrel.2014.08.020.
    Published Version
    http://dx.doi.org/10.1016/j.jconrel.2014.08.020
    Keyword
    Mesoporous silicon; Adeno-associated virus; inflammation; lung; Endothelium; More... Ex vivo perfusion Less...
    Type
    Journal article
    Publisher
    Elsevier
    Citable link to this page
    https://hdl.handle.net/1911/87475
    Rights
    This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.
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    • Bioengineering Publications [632]
    • Faculty Publications [4990]

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    Home | FAQ | Contact Us | Privacy Notice | Accessibility Statement
    Managed by the Digital Scholarship Services at Fondren Library, Rice University
    Physical Address: 6100 Main Street, Houston, Texas 77005
    Mailing Address: MS-44, P.O.BOX 1892, Houston, Texas 77251-1892
    Site Map