Sonoporation: Mechanical DNA delivery by ultrasonic cavitation.
Sonoporation: Mechanical DNA delivery by ultrasonic cavitation.
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DOI：
10.1023/a:1022983907223
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发表时间：
2002-11-01
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影响因子：
--
通讯作者：
Greenleaf, James F.
中科院分区：
文献类型：
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作者：
Miller, Douglas L.;Pislaru, Sorin V.;Greenleaf, James F.
非病毒基因转移方法的发展将是基因治疗手段的一个有价值的补充，特别是对于特定组织体积的局部靶向。超声波可以通过声空化产生包括DNA传递在内的各种非热生物效应。空化气泡可在单个细胞水平上引起细胞死亡或瞬时膜通透性(声学作用)，以及微血管出血和组织结构破坏。为了将基因输送到细胞中，应用声波法需要控制空化活性。许多研究都是使用体外暴露系统进行的，对这种系统来说，空化几乎无处不在。在体内，空化的引发和控制比较困难，但可以通过空化成核剂，如超声造影剂来增强。超声修复术和超声增强的基因传递已被报道用于各种条件，包括低频超声(千赫频率)、碎石机冲击波、HIFU，甚至诊断超声(兆赫频率)。在体外，已经成功地将多种细胞系导入，并伴随着细胞杀伤。在体内，最初的应用是癌症基因治疗和心血管疾病，对癌症来说，杀死细胞可以成为一种有用的同时治疗方法。超声波用于非病毒基因的传递已经在一系列强大的体外和哺乳动物系统中被证明，这为临床医学发展新的基因治疗方法提供了基本的基础和强有力的前景。
Development of nonviral gene transfer methods would be a valuable addition to the gene-therapy armamentarium, particularly for localized targeting of specific tissue volumes. Ultrasound can produce a variety of nonthermal bioeffects via acoustic cavitation including DNA delivery. Cavitation bubbles may induce cell death or transient membrane permeabilization (sonoporation) on a single cell level, as well as microvascular hemorrhage and disruption of tissue structure. Application of sonoporation for gene delivery to cells requires control of cavitation activity. Many studies have been performed using in vitro exposure systems, for which cavitation is virtually ubiquitous. In vivo, cavitation initiation and control is more difficult, but can be enhanced by cavitation nucleation agents, such as an ultrasound contrast agent. Sonoporation and ultrasonically enhanced gene delivery has been reported for a wide range of conditions including low frequency sonication (kilohertz frequencies), lithotripter shockwaves, HIFU, and even diagnostic ultrasound (megahertz frequencies). In vitro, a variety of cell lines has been successfully transfected, with concomitant cell killing. In vivo, initial applications have been to cancer gene therapy, for which cell killing can be a useful simultaneous treatment, and to cardiovascular disease. The use of ultrasound for nonviral gene delivery has been demonstrated for a robust array of in vitro and mammalian systems, which provides a fundamental basis and strong promise for development of new gene therapy methods for clinical medicine.