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体内细胞内质粒 DNA 传递的非接触式磁渗透作用。

Contactless magneto-permeabilization for intracellular plasmid DNA delivery in-vivo.

机构信息

MagneGene, Inc., Laguna Hills, CA, USA.

出版信息

Hum Vaccin Immunother. 2012 Nov 1;8(11):1707-13. doi: 10.4161/hv.21576. Epub 2012 Aug 16.

Abstract

Electroporation, an attractive process for delivering DNA and other molecules into target cells in vivo and in vitro is limited by the necessity of electrodes that need to be in contact with the subject or object to be electroporated. We have used magnetic fields, which do not require material contact with the subject, to temporarily permeabilize cells in guinea pig skin in vivo to enhance uptake and expression of GFP plasmid DNA. The results show for the first time that magnetic fields can trigger a process likely similar to electroporation. In designing the magnetic pulses, our most important criterion was a high rate of change of the magnetic field, based on the principle described by Michael Faraday which is expressed by the formula: E = -dB/dt, (E, electric field, B, magnetic field, t, time). Magnetic fields were generated by a flat electromagnet in a hand-held applicator positioned above the target tissue. The magnetic pulses had a peak magnetic flux density of 4 tesla; 50 pulses were applied in 5 sec. Biphasic magnetic pulses were twice as effective as monophasic pulses and about equally effective as traditional electroporation pulses . Advantages of magnetopermeabilization over electoporation include: No contact between applicator and subject ("contact-less"); no need for invasive, disposable, sterile electrodes ("needle-less"); no pain from needles and reduced overall pain; no known side effects; easier and faster to administer than electroporation; less expensive due to absence of disposables; and, importantly, greater tissue penetration of the magnetic field allowing treatment of anatomical areas inaccessible by electroporation.

摘要

电穿孔是一种将 DNA 和其他分子递送到体内和体外靶细胞的有吸引力的方法,但受到需要与待处理的主体接触的电极的限制。我们使用磁场,不需要与主体接触,来暂时使豚鼠皮肤细胞在体内穿孔,以增强 GFP 质粒 DNA 的摄取和表达。结果首次表明,磁场可以引发类似于电穿孔的过程。在设计磁场脉冲时,我们最重要的标准是磁场的快速变化率,这基于迈克尔·法拉第描述的原理,该原理由公式 E = -dB/dt 表示(E,电场,B,磁场,t,时间)。磁场由位于目标组织上方的手持式应用器中的扁平电磁铁产生。磁场脉冲的峰值磁通密度为 4 特斯拉;在 5 秒内施加 50 个脉冲。双相磁场脉冲比单相脉冲有效两倍,与传统的电穿孔脉冲效果大致相同。磁穿孔相对于电穿孔的优点包括:应用器与主体之间无接触(“无接触”);不需要侵入性、一次性、无菌的电极(“无针”);无针引起的疼痛和总体疼痛减轻;无已知的副作用;比电穿孔更容易和更快地进行管理;由于不需要一次性用品,成本更低;并且,重要的是,磁场的组织穿透更深,允许治疗电穿孔无法到达的解剖区域。

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