Frank Reidy Research Center for Bioelectrics, Old Dominion University, Norfolk, VA 23508, USA.
Hum Gene Ther. 2010 Mar;21(3):357-62. doi: 10.1089/hum.2009.065.
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.
皮肤易于接近，使其成为基因转移方案的极佳靶标。为了充分利用皮肤作为基因转移的靶标，建立高效且可重复的传递系统非常重要。电穿孔是满足该传递标准的有力候选者。皮肤的电穿孔是一种简单、直接的体内方法，可用于传递用于治疗的基因。以前，通过具有相对较大电极之间距离的涂敷器对皮肤进行递送，这会导致明显的肌肉刺激和疼痛。这些涂敷器在控制施加场的方向上也存在局限性。为了解决这个问题，开发了一种由电极阵列组成的系统，该系统缩小了它们之间的距离，并可独立寻址以控制场的方向。将这种新型多电极阵列（MEA）与已建立的电极进行了比较。在大鼠模型中，在用每种电极进行递送后，均观察到可比的报告基因表达。还在豚鼠模型中评估了递送，以确定这种方法在与人类皮肤厚度和结构相似的动物模型中的潜力。结果清楚地表明，有效的递送与电极和选择的参数都有关。与传统电极系统相比，MEA 显著减少了与电场施加相关的肌肉抽搐。这很重要，因为它将促进电穿孔介导的基因传递到皮肤的转化，用于 DNA 疫苗的临床应用或用于癌症或蛋白质缺乏症的治疗。
