Ex vivo adenoviral vector gene delivery results in decreased vector-associated inflammation pre- and post-lung transplantation in the pig.

Ex vivo adenoviral vector gene delivery results in decreased vector-associated inflammation pre- and post-lung transplantation in the pig.
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离体腺病毒载体基因递送可减少猪肺移植前后载体相关的炎症。

DOI:
10.1038/mt.2012.57
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发表时间:
2012
期刊:
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子:
--
通讯作者:
S. Keshavjee
S. Keshavjee
中科院分区:
--
文献类型:
--
作者:
J. Yeung;D. Wagnetz;M. Cypel;M. Rubacha;T. Koike;Yi;Jim Hu;T. Waddell;D. Hwang;Mingyao Liu;S. Keshavjee

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Acellular normothermic ex vivo lung perfusion (EVLP) is a novel method of donor lung preservation for transplantation. As cellular metabolism is preserved during perfusion, it represents a potential platform for effective gene transduction in donor lungs. We hypothesized that vector-associated inflammation would be reduced during ex vivo delivery due to isolation from the host immune system response. We compared ex vivo with in vivo intratracheal delivery of an E1-, E3-deleted adenoviral vector encoding either green fluorescent protein (GFP) or interleukin-10 (IL-10) to porcine lungs. Twelve hours after delivery, the lung was transplanted and the post-transplant function assessed. We identified significant transgene expression by 12 hours in both in vivo and ex vivo delivered groups. Lung function remained excellent in all ex vivo groups after viral vector delivery; however, as expected, lung function decreased in the in vivo delivered adenovirus vector encoding GFP (AdGFP) group with corresponding increases in IL-1β levels. Transplanted lung function was excellent in the ex vivo transduced lungs and inferior lung function was seen in the in vivo group after transplantation. In summary, ex vivo delivery of adenoviral gene therapy to the donor lung is superior to in vivo delivery in that it leads to less vector-associated inflammation and provides superior post-transplant lung function.
非特异性炎症抑制腺病毒介导的肺部基因转移和表达,与特异性获得性免疫反应无关。
DOI: 10.1089/hum.1998.9.15-2207
发表时间: 1998
期刊: Human gene therapy.
影响因子: --
作者:
Otake,K;Ennist,DL;Harrod,K;Trapnell,BC
通讯作者: Trapnell,BC
基因治疗和移植。
DOI: 10.1097/00007890-200005270-00001
发表时间: 2000
期刊: Transplantation
影响因子: 6.2
作者:
Gojo,S;Cooper,DK;Iacomini,J;LeGuern,C
通讯作者: LeGuern,C