Electro-gene transfer to skin using a noninvasive multielectrode array.
Electro-gene transfer to skin using a noninvasive multielectrode array.
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DOI：
10.1016/j.jconrel.2011.01.014
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发表时间：
2011-05-10
期刊：
影响因子：
--
通讯作者：
Heller R
中科院分区：
文献类型：
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作者：
Guo S;Donate A;Basu G;Lundberg C;Heller L;Heller R
由于其大的表面积和易于接近的递送和监测，皮肤是皮肤疾病、疫苗接种和几种代谢紊乱的基因治疗的有吸引力的靶点。通过电穿孔（EP）将DNA递送至皮肤的关键因素是有效表达水平和最小或无组织损伤。在这里，我们评估了非侵入性的多电极阵列（MEA）的基因电转移。在这些研究中，我们使用了豚鼠模型，该模型已被证明具有与人类皮肤相似的厚度和结构。我们的结果表明，在15天内，基因表达显著增加，比单独注射质粒DNA高2至3个对数。此外，可以通过增加处理区域的大小来增强基因表达。仅在皮肤的表皮层中观察到转基因表达细胞。与卡尺或平板电极相比，使用MEA的皮肤EP大大减少了肌肉抽搐，并导致最小和完全可恢复的皮肤损伤。这些结果表明，与MEA的EP可以是一种有效的和非侵入性的皮肤递送方法，与其他EP递送系统相比，不良副作用更少，并且具有良好的临床应用前景。
Because of its large surface area and easy access for both delivery and monitoring, the skin is an attractive target for gene therapy for cutaneous diseases, vaccinations and several metabolic disorders. The critical factors for DNA delivery to the skin by electroporation (EP) are effective expression levels and minimal or no tissue damage. Here, we evaluated the non-invasive multielectrode array (MEA) for gene electrotransfer. For these studies we utilized a guinea pig model, which has been shown to have a similar thickness and structure to human skin. Our results demonstrate significantly increased gene expression 2 to 3 logs above injection of plasmid DNA alone over 15 days. Furthermore, gene expression could be enhanced by increasing the size of the treatment area. Transgene expressing cells were observed exclusively in the epidermal layer of the skin. In contrast to caliper or plate electrodes, skin EP with the MEA greatly reduced muscle twitching and resulted in minimal and completely recoverable skin damage. These results suggest EP with the MEA can be an efficient and non-invasive skin delivery method with less adverse side effects than other EP delivery systems and promising clinical applications.