<br>电转染作为基因传递的非病毒方法的最新进展,Molecular Pharmaceutics

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电转染作为基因传递的非病毒方法的最新进展
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2018-06-11 00:00:00 , DOI: 10.1021/acs.molpharmaceut.8b00207
Lisa D Cervia ₁ , Fan Yuan ₁

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电转染 (ET) 是一种在体外和体内将各种类型的分子递送到细胞中的非病毒方法。已经进行了近 90 项涉及使用 ET 的临床试验，其中大约一半与癌症治疗有关。特别是，ET对于癌症免疫基因治疗来说是一项有吸引力的技术，因为仅用电脉冲处理细胞就可以诱导针对实体瘤的免疫反应，并且通过编码治疗基因的质粒DNA（pDNA）的ET可以进一步增强该反应。与其他基因递送方法相比，ET具有几个独特的优势。它在临床应用中相对便宜、灵活且安全，并且仅将裸露的 pDNA 引入细胞中，而不使用额外的化学物质或病毒。然而，ET 的效率仍然较低，部分原因是 ET 在细胞中的生物学机制仍不清楚。在之前的研究中，人们认为 pDNA 通过电脉冲产生的瞬时孔进入细胞。因此，该技术通常称为电穿孔。然而，最近的发现表明内吞作用在电转染 pDNA 的细胞摄取和细胞内运输中发挥着重要作用。本文将讨论ET生物学机制研究的最新进展以及该领域的未来研究方向。了解细胞中 pDNA 转运的机制对于开发提高肿瘤基因传递效率的新策略至关重要。

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Current Progress in Electrotransfection as a Nonviral Method for Gene Delivery

Electrotransfection (ET) is a nonviral method for delivery of various types of molecules into cells both in vitro and in vivo. Close to 90 clinical trials that involve the use of ET have been performed, and approximately half of them are related to cancer treatment. Particularly, ET is an attractive technique for cancer immunogene therapy because treatment of cells with electric pulses alone can induce immune responses to solid tumors, and the responses can be further enhanced by ET of plasmid DNA (pDNA) encoding therapeutic genes. Compared to other gene delivery methods, ET has several unique advantages. It is relatively inexpensive, flexible, and safe in clinical applications, and introduces only naked pDNA into cells without the use of additional chemicals or viruses. However, the efficiency of ET is still low, partly because biological mechanisms of ET in cells remain elusive. In previous studies, it was believed that pDNA entered the cells through transient pores created by electric pulses. As a result, the technique is commonly referred to as electroporation. However, recent discoveries have suggested that endocytosis plays an important role in cellular uptake and intracellular transport of electrotransfected pDNA. This review will discuss current progresses in the study of biological mechanisms underlying ET and future directions of research in this area. Understanding the mechanisms of pDNA transport in cells is critical for the development of new strategies for improving the efficiency of gene delivery in tumors.

更新日期：2018-06-11

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