Inovio Pharmaceuticals, Inc., San Diego, CA, USA.
The Scripps Research Institute, Core Microscopy Facility, La Jolla, CA, USA.
Gene Ther. 2017 Dec;24(12):757-767. doi: 10.1038/gt.2017.96. Epub 2017 Nov 6.
DNA vaccines delivered using electroporation (EP) have had clinical success, but these EP methods generally utilize invasive needle electrodes. Here, we demonstrate the delivery and immunogenicity of a DNA vaccine into subcutaneous adipose tissue cells using noninvasive EP. Using finite element analysis, we predicted that plate electrodes, when oriented properly, could effectively concentrate the electric field within adipose tissue. In practice, these electrodes generated widespread gene expression persisting for at least 60 days in vivo within interscapular subcutaneous fat pads of guinea pigs. We then applied this adipose-EP protocol to deliver a DNA vaccine coding for an influenza antigen into guinea pigs. The resulting host immune responses elicited were of a similar magnitude to those achieved by skin delivery with EP. The onset of the humoral immune response was more rapid when the DNA dose was spread over multiple injection sites, and increasing the voltage of the EP device increased the magnitude of the immune response. This study supports further development of EP protocols delivering gene-based therapies to subcutaneous fat.
电穿孔（EP）递送的 DNA 疫苗已在临床上取得成功，但这些 EP 方法通常使用侵入性的针状电极。在这里，我们使用非侵入性 EP 演示了 DNA 疫苗递送至皮下脂肪组织细胞的方法和其免疫原性。通过有限元分析，我们预测，当板状电极正确定向时，可以有效地将电场集中在脂肪组织内。在实践中，这些电极在体内至少持续 60 天产生了广泛的基因表达，在豚鼠肩胛间皮下脂肪垫中。然后，我们将这种脂肪组织-EP 方案应用于向豚鼠递送编码流感抗原的 DNA 疫苗。所引起的宿主免疫反应的大小与 EP 皮肤递送所产生的反应相当。当 DNA 剂量分布在多个注射部位时，体液免疫反应的开始更快，并且增加 EP 设备的电压会增加免疫反应的幅度。这项研究支持进一步开发将基因治疗递送至皮下脂肪的 EP 方案。
