Bloquel Carole, Fabre Emmanuelle, Bureau Michel Francis, Scherman Daniel
Laboratoire de Pharmacologie Chimique et Génétique, U266 INSERM FRE 2463 CNRS, Faculté de Pharmacie Paris 5/ENSCP, 4 avenue de l'Observatoire, 75270 Paris cedex 06, France.
J Gene Med. 2004 Feb;6 Suppl 1:S11-23. doi: 10.1002/jgm.508.
In vivo electrotransfer is a physical method of gene delivery in various tissues and organs, relying on the injection of a plasmid DNA followed by electric pulse delivery. The importance of the association between cell permeabilization and DNA electrophoresis for electrotransfer efficiency has been highlighted. In vivo electrotransfer is of special interest since it is the most efficient non-viral strategy of gene delivery and also because of its low cost, easiness of realization and safety. The potentiality of this technique can be further improved by optimizing plasmid biodistribution in the targeted organ, plasmid structure, and the design of the encoded protein. In particular, we found that plasmids of smaller size were electrotransferred more efficiently than large plasmids. It is also of importance to study and understand kinetic expression of the transgene, which can be very variable, depending on many factors including cellular localization of the protein, physiological activity and regulation. The most widely targeted tissue is skeletal muscle, because this strategy is not only promising for the treatment of muscle disorders, but also for the systemic secretion of therapeutic proteins. Vaccination and oncology gene therapy are also major fields of application of electrotransfer, whereas application to other organs such as liver, brain and cornea are expanding. Many published studies have shown that plasmid electrotransfer can lead to long-lasting therapeutic effects in various pathologies such as cancer, blood disorders, rheumatoid arthritis or muscle ischemia. DNA electrotransfer is also a powerful laboratory tool to study gene function in a given tissue.
体内电穿孔是一种在各种组织和器官中进行基因递送的物理方法，它依赖于注射质粒DNA，随后进行电脉冲递送。细胞通透性与DNA电泳之间的关联对电穿孔效率的重要性已得到强调。体内电穿孔备受关注，因为它是最有效的非病毒基因递送策略，而且成本低、易于实现且安全。通过优化质粒在靶器官中的生物分布、质粒结构以及编码蛋白的设计，可以进一步提高该技术的潜力。特别是，我们发现较小尺寸的质粒比大质粒电穿孔效率更高。研究和理解转基因的动力学表达也很重要，其表达可能因许多因素而有很大差异，包括蛋白质的细胞定位、生理活性和调控。最广泛靶向的组织是骨骼肌，因为这种策略不仅有望治疗肌肉疾病，还可用于治疗性蛋白质的全身分泌。疫苗接种和肿瘤基因治疗也是电穿孔的主要应用领域，而其在肝脏、大脑和角膜等其他器官的应用也在不断扩展。许多已发表的研究表明，质粒电穿孔可在癌症、血液疾病、类风湿性关节炎或肌肉缺血等各种病症中产生持久的治疗效果。DNA电穿孔也是研究特定组织中基因功能的强大实验室工具。
