Electroporation: a promising method for the nonviral delivery of DNA vaccines in humans?

Lars Frelin, Anette Brass, Gustaf Ahlén, Erwin Daniel Brenndörfer, Margaret Chen, Matti Sällberg
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引用次数: 21

Abstract

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.

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电穿孔:一种很有前途的人类非病毒递送DNA疫苗的方法?
毫无疑问,DNA疫苗取得商业成功的主要障碍是交付。如果不能使递送变得简单、廉价和有效,DNA疫苗可能不会成为人类使用的可行选择。许多临床试验已经证实,标准的针头和注射器根本无法完成这项工作,即在细胞内传递DNA有效载荷。认识到这一缺陷后,研究人员开发了几种新的DNA疫苗递送方法。特别是,最初用于体外使用的新型输送装置已应用于体内输送。这些包括粒子轰击或生物传递,以及体内电穿孔(EP)。重要的是,这两种技术似乎都克服了体型障碍,这意味着它们在老鼠和更大的动物身上都有效。在体内,EP具有DNA摄取改善、抗原表达增加和局部炎症的主要特征。这些因素对于使DNA疫苗在更大的宿主中有效至关重要。通过体内EP传递DNA疫苗的早期临床试验数据显示出谨慎的希望。因此,我们可能正在进入一个DNA疫苗接种的新时代,我们开始在人类身上看到临床效果;然而,随着疫苗变得更加有效,这些也可能伴随着副作用。
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Drug news & perspectives
Drug news & perspectives 医学-药学
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Osteopontin. Trends in medicinal chemistry. Molecule of the Month. The significance of GlgE as a new target for tuberculosis. Inhibition of potassium currents as a pharmacologic target for investigation in chronic lymphocytic leukemia.
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