Trollet C, Bloquel C, Scherman D, Bigey P
Inserm, U640, Paris, F-75006 France.
Curr Gene Ther. 2006 Oct;6(5):561-78. doi: 10.2174/156652306778520656.
An efficient and safe method to deliver DNA in vivo is a requirement for several purposes, such as study of gene function and gene therapy applications. Among the different non-viral delivery methods currently under investigation, in vivo DNA electrotransfer has proven to be one of the most efficient and simple. This technique is a physical method of gene delivery consisting in local application of electric pulses after DNA injection. Although this technique can be applied to almost any tissue of a living animal, including tumors, skin, liver, kidney, artery, retina, cornea or even brain, this review will focus on electrotransfer of plasmid DNA into skeletal muscle and its possible uses in gene therapy, vaccination, or functional studies. Skeletal muscle is a good target for electrotransfer of DNA as it is: a large volume easily accessible, an endocrine organ capable of expressing several local and systemic factors, and muscle fibres as post-mitotic cells have a long lifespan that allows long-term gene expression. In this review, we describe the mechanism of DNA electrotransfer, we assess toxicity and safety considerations related to this technique, and we focus on important therapeutic applications of electrotransfer demonstrated in animal models in recent years.
为了实现多种目的,如基因功能研究和基因治疗应用,需要一种高效且安全的体内DNA递送方法。在目前正在研究的不同非病毒递送方法中,体内DNA电穿孔已被证明是最有效且最简单的方法之一。该技术是一种基因递送的物理方法,即在注射DNA后局部施加电脉冲。尽管这种技术几乎可以应用于活体动物的任何组织,包括肿瘤、皮肤、肝脏、肾脏、动脉、视网膜、角膜甚至大脑,但本综述将聚焦于将质粒DNA电穿孔导入骨骼肌及其在基因治疗、疫苗接种或功能研究中的可能用途。骨骼肌是DNA电穿孔的良好靶点,因为它:体积大且易于触及,是一个能够表达多种局部和全身因子的内分泌器官,并且作为有丝分裂后细胞的肌纤维寿命长,这使得基因能够长期表达。在本综述中,我们描述了DNA电穿孔的机制,评估了与该技术相关的毒性和安全性问题,并聚焦于近年来在动物模型中证明的电穿孔的重要治疗应用。