Frelin Lars, Brass Anette, Ahlén Gustaf, Brenndörfer Erwin Daniel, Chen Margaret, Sällberg Matti
Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Drug News Perspect. 2010 Dec;23(10):647-53. doi: 10.1358/dnp.2010.23.10.1513492.
The without a doubt major obstacle for making DNA vaccines a commercial success is delivery. If delivery cannot be made simple, cheap and effective, DNA vaccines may not become a viable option for human use. Numerous clinical trials have confirmed that a standard needle and syringe simply do not do the job, i.e., delivering the DNA payload inside the cell. Having recognized this shortcoming, investigators have developed several new approaches for DNA vaccine delivery. In particular, new types of delivery devices, originally intended for in vitro use, have been applied for in vivo delivery. These include particle bombardment or biolistic delivery, and in vivo electroporation (EP). Importantly, both techniques seem to overcome the size barrier, meaning that they work in both mice and larger animals. In vivo EP has the key features of improved DNA uptake, increased antigen expression and a local inflammation. These factors are essential to make DNA vaccines effective in a larger host. Early data from clinical trials with DNA vaccines delivered by in vivo EP are cautiously promising. Thus, we may be entering a new era of DNA vaccination where we start to see clinical effects in humans; however, these may also be accompanied by side effects, as the vaccines become more effective.
毫无疑问，使DNA疫苗取得商业成功的主要障碍是递送问题。如果不能实现简单、廉价且有效的递送，DNA疫苗可能无法成为适用于人类的可行选择。大量临床试验证实，标准的针头和注射器根本无法完成这项工作，即无法将DNA有效载荷递送至细胞内。认识到这一缺点后，研究人员开发了几种新的DNA疫苗递送方法。特别是，一些原本用于体外的新型递送装置已被应用于体内递送。这些方法包括粒子轰击或生物弹道递送，以及体内电穿孔（EP）。重要的是，这两种技术似乎都克服了尺寸障碍，也就是说它们在小鼠和大型动物中均有效。体内电穿孔具有改善DNA摄取、增加抗原表达和引发局部炎症等关键特性。这些因素对于使DNA疫苗在更大的宿主中发挥作用至关重要。来自体内电穿孔递送DNA疫苗的临床试验的早期数据显示出谨慎的前景。因此，我们可能正在进入DNA疫苗接种的新时代，开始看到其在人类身上产生临床效果；然而，随着疫苗变得更加有效，这些效果可能也会伴随着副作用。
