Cemazar M, Golzio M, Sersa G, Rols M P, Teissié J
IPBS CNRS, UMR 5089, 205, Route de Narbonne, 31077 Toulouse Cedex, France.
Curr Pharm Des. 2006;12(29):3817-25. doi: 10.2174/138161206778559740.
Electropulsation (electroporation) is a physical method for delivery of various molecules into the cells in vitro and in vivo. It is an expanding field due to its applicability in cancer therapy, where combined application of electric pulses and chemotherapeutic drugs is used for treatment of cutaneous and subcutaneous nodules of different malignancies. Another application of electropulsation in vivo is electrogene therapy, where after injection of naked plasmid DNA and delivery of electric pulses directly to the tissue the expression of gene of interest can be obtained. However, the transfection efficiency of this methodology in vivo is still lower than with viral vectors. Nevertheless, due to the lack of immunogenicity of the method, easiness of the preparation of large quantities of endotoxin free plasmid DNA, control and reproducibility of the method and the development of electropulsators approved for the clinical use, electrically-assisted nucleic-acid delivery holds a great potential for the clinical application. This aim of this minireview is to critically discuss the main limitations and obstacles associated with electrogene therapy and the failures and problems as well as the successes. Topics on electric field distribution in the tissue, electrode geometries, construction of plasmid, modulation of extracellular space, tissue damage, pro-inflammatory and immune response as well as blood flow modification associated with application of electric pulses and injection of naked DNA are presented with possible directions how to overcome these limitations. Furthermore, for successful electrogene therapy in clinical setting it is of utmost importance to elucidate the mechanisms of DNA transfer into the cells of tissues in vivo. This will enable appropriate selection of electric pulse parameters and plasmid DNA constructs for each particular intended use. In the long run, this review should encourage other scientists to consider electrically assisted gene delivery for gene therapy as it matures.
电脉冲（电穿孔）是一种在体外和体内将各种分子递送至细胞的物理方法。由于其在癌症治疗中的适用性，它是一个不断发展的领域，在癌症治疗中，电脉冲与化疗药物联合应用用于治疗不同恶性肿瘤的皮肤和皮下结节。电脉冲在体内的另一个应用是电基因治疗，即在注射裸质粒DNA并将电脉冲直接递送至组织后，可以获得感兴趣基因的表达。然而，这种方法在体内的转染效率仍然低于病毒载体。尽管如此，由于该方法缺乏免疫原性、易于制备大量无内毒素的质粒DNA、方法的可控性和可重复性以及已批准用于临床的电脉冲发生器的开发，电辅助核酸递送在临床应用中具有巨大潜力。本综述的目的是批判性地讨论与电基因治疗相关的主要局限性和障碍以及失败、问题和成功之处。介绍了与电脉冲应用和裸DNA注射相关的组织中电场分布、电极几何形状、质粒构建、细胞外空间调节、组织损伤、促炎和免疫反应以及血流改变等主题，并提出了克服这些局限性的可能方向。此外，为了在临床环境中成功进行电基因治疗，阐明DNA在体内组织细胞中的转移机制至关重要。这将能够为每种特定的预期用途适当选择电脉冲参数和质粒DNA构建体。从长远来看，随着电辅助基因递送技术的成熟，本综述应鼓励其他科学家考虑将其用于基因治疗。
