MICROBUBBLE STABILITY IS A MAJOR DETERMINANT OF THE EFFICIENCY OF ULTRASOUND AND MICROBUBBLE MEDIATED IN VIVO GENE TRANSFER
MICROBUBBLE STABILITY IS A MAJOR DETERMINANT OF THE EFFICIENCY OF ULTRASOUND AND MICROBUBBLE MEDIATED IN VIVO GENE TRANSFER
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DOI：
10.1016/j.ultrasmedbio.2008.12.015
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发表时间：
2009-06-01
影响因子：
2.9
通讯作者：
Wells, Dominic J.
中科院分区：
文献类型：
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作者：
Alter, Julia;Sennoga, Charles A.;Wells, Dominic J.
在寻找一种有效的非病毒基因治疗方法，用于治疗心脏和骨骼肌的遗传性疾病，如杜氏肌营养不良症，超声结合对比增强微泡已成为一个有前途的工具，安全和位点特异性增强基因传递。事实上，微泡增强的基因转移（MBGT）已经研究了各种各样的目标网站使用报告和治疗基因。虽然一系列不同的微泡已被用于MBGT研究，它们的效率比较是困难的，因为微泡浓度和用于应用的超声设置变化很大。迄今为止，只有两项研究尝试直接比较市售微泡，并且都得出结论，并非所有微泡都显示出与MBGT相同的效率。到目前为止，原因尚不清楚。在这里，三个市售的微泡-Optison，SonoVue和Sonazoid-的效率进行了分析，以了解微泡的特性，它们作为一个有效的增强体内基因转移的功能是重要的。在这项研究中，质粒DNA或反义寡核苷酸通过全身注射MBGT递送，集中在心脏。以相等浓度的三种微泡将基因递送至心脏表明，与SonoVue相比，Optison和Sonazoid在MBGT中更有效，SonoVue显示出最弱的基因转移至心肌。这些微泡的性质的调查表明，尺寸和壳的组成并不直接影响MBGT，而在超声保持稳定性增加的微泡显示出更好的MBGT结果比那些降解更快。此外，用于MBGT的微泡浓度也被发现是影响MBGT效率的重要因素。总之，微泡的稳定性被证明是其在MBGT中的性能的主要影响因素，正如所使用的微泡的浓度一样。这些发现强调了详细调查微泡的性质的重要性，以允许生产专为MBGT的最佳性能而设计的微泡。（电子邮件：d.威尔斯@ imperial.ac.uk）（C）2009年世界医学和生物学超声联合会。
In the search for an efficient nonviral gene therapy approach for the treatment of genetic disorders of cardiac and skeletal muscle such as Duchenne muscular dystrophy, ultrasound in combination with contrast enhancing microbubbles has emerged as a promising tool for safe and site-specific enhancement of gene delivery. Indeed, microbubble-enhanced gene transfer (MBGT) has been investigated for a wide variety of target sites using both reporter and therapeutic genes. Although a range of different microbubbles have been used for MBGT studies, comparison of their efficiencies is difficult because microbubble concentration and the ultrasound settings used for the application vary considerably. Only two studies to date have attempted a direct comparison of commercially available microbubbles, and both concluded that not all microbubbles show the same efficiencies with MBGT. Thus far, the reason for this is unclear. Here, the efficiency of three commercially available microbubbles-Optison, SonoVue and Sonazoid-was analyzed to understand the microbubble properties that are important for their function as an effective enhancer for gene transfer in vivo. In this study, plasmid DNA or antisense oligonucleotides were delivered by systemic injection with MBGT, focused on the heart. Gene delivery to the heart with equalized concentrations of the three microbubbles showed that Optison and Sonazoid are more efficient in MBGT compared with SonoVue, which showed the weakest gene transfer to the myocardium. Investigations into the properties of these microbubbles showed that size and shell composition did not directly influence MBGT, whereas the microbubbles with increased stability in an ultrasound held showed better MBGT results than those degrading faster. Moreover, the microbubble concentration used for MBGT was also found to be an important factor influencing the efficiency of MBGT. In conclusion, the stability of a microbubble was shown to be a major influential factor for its performance in MBGT, as is the concentration of the microbubbles used. These findings emphasize the importance of detailed investigations into the properties of microbubbles to allow the production of a microbubble specifically designed for optimum performance with MBGT. (E-mail: d.wells@imperial.ac.uk) (C) 2009 World Federation for Ultrasound in Medicine & Biology.