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具有闭环再循环的原位心脏隔离: 最佳心脏基因转移的黄金标准?

迈克 尔·, 安东 尼·, 查尔 斯·
西奈山伊坎医学院

摘要


将编码治疗基因的核酸材料输送到心脏的概念已经从假设转变为各种高潜力的临床应用。然而,尽管有希望,
但由于临床中存在的几个问题,尚未实现所取得的成果。这些已确定的问题之一是需要一种有效的递送方法,以促进
完全的强心作用并最大限度地减少附带效应。影响基因传递的最需要改进的其他参数已确定如下:(1)增加载体在冠
状动脉循环中的接触时间以允许转移,(2)维持血管内流速和灌注压力以促进适当的动力学,(3)调节细胞通透性以
提高摄取效率,并且一旦进入细胞,(4)增强转染心脏细胞内的转录和翻译,以及,(5)获得全局基因分布以获得最
大功效。最近有人假设,使用心肺分流术可以促进心脏选择性基因转移,并允许在孤立的“闭环”再循环模型中将载
体递送到停滞的心脏中。该系统被命名为具有再循环递送的分子心脏手术(MCARD)。这种方法的关键组成部分包
括:将心脏与全身器官隔离,通过冠状脉管系统的载体多次循环再循环,以及从冠状动脉循环中去除残余载体以最大
限度地减少侧支表达。MCARD等手术方法特有的这些属性可以有效提高冠状动脉血管系统中的载体转导效率。

关键词


基因治疗;循环输送的分子心脏手术;心脏隔离

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参考


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DOI: http://dx.doi.org/10.12361/2705-0459-04-09-107617

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