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用于体内DNA递送的哺乳动物真皮组织的压电透化可增强蛋白质表达并提高免疫原性。

Piezoelectric permeabilization of mammalian dermal tissue for in vivo DNA delivery leads to enhanced protein expression and increased immunogenicity.

作者信息

Broderick Kate E, Kardos Thomas, McCoy Jay R, Fons Michael P, Kemmerrer Stephen, Sardesai Niranjan Y

机构信息

Inovio Pharmaceuticals, Inc., San Diego, CA USA.

出版信息

Hum Vaccin. 2011 Jan-Feb;7 Suppl:22-8. doi: 10.4161/hv.7.0.14559. Epub 2011 Jan 1.

DOI:10.4161/hv.7.0.14559
PMID:21263230
Abstract

Electropermeabilization of mammalian cells is a technique that has been used for the delivery of therapeutics, such as DNA plasmids or DNA vaccines. Typically, delivery via electropermeabilization occurs through injection of the substance into the tissue of interest followed by the insertion of electrodes at the site and the application of brief electrical pulses. Here we detail a novel and innovative contactless electropermeabilization method to deliver DNA plasmids to dermal tissue in vivo. This process has the advantage of eliminating the insertion of additional needles that serve as electrodes to facilitate the application of electric pulses in conventional electroporation processes. Plasmid encoding GFP was injected into guinea pig skin and pulsed with the novel contactless electropermeabilization method. Three days following treatment, robust GFP expression was observed on the skin of pulsed animals. Strong humoral immune responses were also achieved when a DNA vaccine expressing the influenza antigen NP was delivered and pulsed using the novel device in comparison to naked injection alone. This delivery method has the advantage of being contactless and suggests that gene transfer via this mode warrants further development.

摘要

哺乳动物细胞的电通透化是一种已用于递送治疗剂(如DNA质粒或DNA疫苗)的技术。通常,通过电通透化进行递送是将物质注射到感兴趣的组织中,然后在该部位插入电极并施加短暂的电脉冲。在此,我们详细介绍一种新颖的非接触式电通透化方法,用于在体内将DNA质粒递送至皮肤组织。该过程的优点是无需插入额外的作为电极的针,而在传统电穿孔过程中这些针用于便于施加电脉冲。将编码绿色荧光蛋白(GFP)的质粒注射到豚鼠皮肤中,并采用新型非接触式电通透化方法施加脉冲。治疗三天后,在接受脉冲处理的动物皮肤上观察到了强烈的绿色荧光蛋白表达。与单独的裸注射相比,当使用该新型装置递送并脉冲处理表达流感抗原核蛋白(NP)的DNA疫苗时,也产生了强烈的体液免疫反应。这种递送方法具有非接触式的优点,表明通过这种方式进行基因转移值得进一步研究。

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