Arterial gene transfer using pure DNA applied directly to a hydrogel-coated angioplasty balloon.
Arterial gene transfer using pure DNA applied directly to a hydrogel-coated angioplasty balloon.
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使用直接应用于水凝胶涂层血管成形术球囊的纯 DNA 进行动脉基因转移。
DOI：
10.1089/hum.1993.4.6-749
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发表时间：
1993
影响因子：
4.2
通讯作者：
Isner,JM
中科院分区：
文献类型：
--
作者：
Riessen,R;Rahimizadeh,H;Blessing,E;Takeshita,S;Barry,JJ;Isner,JM
直接动脉基因转移先前已使用双球囊导管和穿孔球囊实现，在大多数情况下通过使用阳离子脂质体或病毒载体来促进。然而，这些基因递送系统已受到与功效和/或安全性相关的问题的损害，并且此外需要独立于基因转移来进行血管成形术。我们研究了在球囊血管成形术期间通过将裸露的遗传物质从应用于标准血管成形术球囊的薄薄的水凝胶聚合物涂层递送来进行动脉基因转移的可能性。将萤光素酶 DNA 应用于水凝胶气球，在兔动脉中进行转染。在三种不同的模型中测试转染后3天的荧光素酶表达：（i）器官培养模型（n=10）； (ii) 手术暴露颈动脉（n = 14）； (iii) 使用经皮入路的髂外动脉 (n= 13)。使用核特异性 β-半乳糖苷酶 (β-gal) 编码基因进行补充转染 (n= 3)，旨在确定动脉转染位点。所有转染荧光素酶基因的兔动脉（37/37；100%）均表达荧光素酶活性。无论是在手术暴露的颈动脉中还是在经皮转染的髂外动脉中，体内实现的基因表达在数量上与器官培养模型中实现的相似。将充气持续时间从 30 分钟减少到 1 分钟对转染效率没有统计学上的显着影响。据记录，基因表达在经皮转染后可持续长达 14 天。对转染核特异性 β-gal 的动脉的分析表明，内膜和内膜下位点存在转基因。这些结果表明，使用应用于涂有水凝胶的标准血管成形术导管球囊的DNA，无需脂质体或病毒载体即可成功进行血管基因转移。使用水凝胶涂层球囊的经皮转染可以使基因转移与血管成形术本身同时进行，即使充气时间短至 1 分钟。
Direct arterial gene transfer has been previously achieved using double-balloon catheters and perforated balloons, in most cases facilitated by the use of cationic liposomes or viral vectors. These gene delivery systems, however, have been compromised by issues relating to efficacy and/or safety, and furthermore require that angioplasty be performed independent of gene transfer. We investigated the possibility that arterial gene transfer might be performed during balloon angioplasty by delivery of naked genetic material from a thin coat of hydrogel polymer applied to a standard angioplasty balloon. Transfections with luciferase DNA applied to a hydrogel balloon were performed in rabbit arteries. Luciferase expression 3 days after transfection was tested in three different models: (i) an organ culture model (n= 10); (ii) surgically exposed carotid arteries (n= 14); and (iii) external iliac arteries using a percutaneous approach (n= 13). Supplementary transfections (n= 3), intended to identify the site of arterial transfection, were performed using the gene encoding for nuclear-specific β-galactosidase (β-gal). All rabbit arteries transfected with the luciferase gene (37/37; 100%) expressed luciferase activity. Gene expression achievedin vivo, either in the surgically exposed carotid arteries or in the external iliac arteries transfected percutaneously, was quantitatively similar to that achieved in the organ culture model. Reduction in the duration of inflation from 30 min to 1 min had no statistically significant impact on transfection efficiency. Gene expression was documented to persist up to 14 days post percutaneous transfection. Analysis of arteries transfected with nuclear-specific β-gal showed the presence of the transgene in intimal and subintimal sites. These results demonstrate that vascular gene transfer can be performed successfully without liposomes or viral vectors using DNA applied to a standard angioplasty catheter balloon coated with hydrogel. Percutaneous transfection with a hydrogel-coated balloon permits gene transfer coincident with the angioplasty procedure itself, even with inflations as short as 1 min.