Li Shulin, Benninger Michael
Department of Otolaryngology/Head and Neck Surgery, Henry Ford Health System, 2799 W. Grand Blvd., Detroit, MI 48202, USA.
Curr Gene Ther. 2002 Feb;2(1):101-5. doi: 10.2174/1566523023348183.
Muscle is a convenient and accessible site for non-viral gene delivery, which can manufacture gene products and provide a long-duration of gene expression. The level of gene expression after administration of naked DNA plasmid or polymer-formulated DNA plasmid containing a reporter gene to muscle via syringe injection, however, is very low. As a result, no significant therapeutic effect can be detected after saline- or polymer-mediated gene delivery into muscle. In 1998, investigators published a striking new approach--electrotransfection--for intramuscular gene delivery (now commonly referred to as electroporation or electroinjection). Electroporation of a non-viral gene into the muscles of small animals has increased the level of gene expression by as much as two orders of magnitude, which is comparable to levels achieved with adenoviral gene delivery. Three years later, intramuscular electroporation gene delivery technology has blossomed. Treatments for different diseases using this approach in animal models have been reported. In this review, I discuss the applications of intramuscular electroporation gene therapy to treat malignancies, renal disease, and anemia, and to prevent drug toxicity to sensory nerves.
肌肉是进行非病毒基因递送的便利且易操作的部位，它能够制造基因产物并实现长时间的基因表达。然而，通过注射器将裸DNA质粒或含有报告基因的聚合物配方DNA质粒注射到肌肉后，基因表达水平非常低。因此，在通过盐水或聚合物介导将基因递送至肌肉后，无法检测到明显的治疗效果。1998年，研究人员发表了一种用于肌肉内基因递送的全新显著方法——电转染（现在通常称为电穿孔或电注射）。将非病毒基因电穿孔导入小动物的肌肉中，可使基因表达水平提高多达两个数量级，这与腺病毒基因递送所达到的水平相当。三年后，肌肉内电穿孔基因递送技术蓬勃发展。已经报道了在动物模型中使用这种方法治疗不同疾病的情况。在这篇综述中，我将讨论肌肉内电穿孔基因疗法在治疗恶性肿瘤、肾脏疾病和贫血以及预防药物对感觉神经的毒性方面的应用。
