Electrically Mediated Delivery of Plasmid DNA to the Skin, Using a Multielectrode Array
Electrically Mediated Delivery of Plasmid DNA to the Skin, Using a Multielectrode Array
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DOI：
10.1089/hum.2009.065
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发表时间：
2010-03-01
影响因子：
4.2
通讯作者：
Jaroszeski, Mark J.
中科院分区：
文献类型：
--
作者：
Heller, Richard;Cruz, Yolmari;Jaroszeski, Mark J.
皮肤的易接近性使其成为基因转移方案的极好靶点。为了充分利用皮肤作为基因转移的靶点，重要的是建立一个有效的和可重复的递送系统。电穿孔是满足该递送标准的强有力的候选者。皮肤电穿孔是一种简单、直接的体内基因传递方法。以前，通过电极之间具有相对较大距离的施用器来执行向皮肤的递送，导致显著的肌肉刺激和疼痛。这些施加器在控制施加场的方向性方面也有局限性。为了解决这个问题，开发了一种由电极阵列组成的系统，该电极阵列减小了它们之间的距离并且可独立寻址以用于场的方向控制。这种新的多电极阵列（MEA）与已建立的电极进行了比较。在大鼠模型中，在用每个电极递送后观察到相当的报告基因表达。还在豚鼠模型中评价了递送，以确定这种方法在皮肤厚度和结构类似于人类皮肤的动物模型中的潜力。结果清楚地表明，有效递送与所选择的电极和参数两者有关。与常规电极系统相比，使用MEA，与电场的应用相关的肌肉抽搐显著减少。这是重要的，因为它将促进电穿孔介导的基因递送到皮肤的翻译，用于DNA疫苗的临床使用或用于癌症或蛋白质缺陷的治疗。
The easy accessibility of skin makes it an excellent target for gene transfer protocols. To take full advantage of skin as a target for gene transfer, it is important to establish an efficient and reproducible delivery system. Electroporation is a strong candidate to meet this delivery criterion. Electroporation of the skin is a simple, direct, in vivo method to deliver genes for therapy. Previously, delivery to the skin was performed by means of applicators with relatively large distances between electrodes, resulting in significant muscle stimulation and pain. These applicators also had limitations in controlling the directionality of the applied field. To resolve this issue, a system consisting of an array of electrodes that decreased the distance between them and that were independently addressable for directional control of the field was developed. This new multielectrode array (MEA) was compared with an established electrode. In a rat model, comparable reporter expression was seen after delivery with each electrode. Delivery was also evaluated in a guinea pig model to determine the potential of this approach in an animal model with skin thickness and structure similar to human skin. The results clearly showed that effective delivery was related to both the electrode and the parameters chosen. With the MEA, the muscle twitching associated with application of electric fields was notably reduced compared with conventional electrode systems. This is important, as it will facilitate the translation of electroporation-mediated gene delivery to skin for clinical use with DNA vaccines or for therapies for cancer or protein deficiencies.