Spinal gene transfer using ultrasound and microbubbles
Spinal gene transfer using ultrasound and microbubbles
复制标题
DOI：
10.1016/j.jconrel.2006.10.026
复制
发表时间：
2007-02-12
影响因子：
10.8
通讯作者：
Kodama, Tetsuya
中科院分区：
文献类型：
--
作者：
Takahashi, Masahiko;Kido, Kanta;Kodama, Tetsuya
脊柱基因疗法是治疗各种脊柱相关疾病的有前途的选择。之前的几项使用病毒载体的研究报告了治疗基因成功转移到脊髓神经系统中。然而，由于与病毒的使用相关的相当大的免疫原性，非病毒基因转移仍需要开发。一种可能的方法是结合使用超声波和回声对比微泡。本研究表明该方法可用于鞘内靶向基因递送。我们通过针刺法在小鼠下腰椎间隙鞘内注射荧光素酶编码的质粒 DNA 和市售白蛋白微泡的混合物。随后对腰椎进行经皮超声处理显着增强了超声处理区域背侧脑膜细胞中的荧光素酶表达（通过成像荧光素生物发光进行分析）。目前的脊柱干预措施没有引起明显的神经损伤。除了超声波和微泡联合使用的一般好处外，我们的方法还可以提供一些特定于脊髓基因转染的优势，包括简单经皮硬脑膜穿刺的微创性、由于超声波通过椎骨解剖孔的通道有限而具有的靶向性，以及可能的旁分泌治疗分子向脊髓神经系统的传递。 (c) 2006 Elsevier B.V. 保留所有权利。
Spinal gene therapy is a promising option for treating various spinal-related disorders. Several previous studies using viral vectors reported successful transfer of therapeutic genes into the spinal nerve system. However, because of the considerable immunogenicity related to the use of viruses, non-viral gene transfer still needs to be developed. One possible approach is the combined use of ultrasound and echo-contrast microbubbles. The present study shows that this method can be applied for targeted intrathecal gene delivery. We intrathecally injected a mixture of plasmid-DNA encoded with luciferase and commercially available albumin microbubbles by needle puncture at the lower lumbar intervertebral space in mice. Subsequent percutaneous ultrasonication on the lumbar vertebrae significantly enhanced the luciferase expression, analyzed by imaging luciferin bioluminescence, in the dorsal meningeal cells at the insonated region. No apparent neurological damages were induced by the present spinal interventions. In addition to the general benefits of the combined use of ultrasound and microbubbles, our approach can offer some advantages specific to spinal gene transfection including minimal invasiveness of simple percutancous dural puncture, targetability due to the limited access of ultrasound waves through anatomical apertures of the vertebrae, and possible paracrine delivery of therapeutic molecules to the spinal nerve system. (c) 2006 Elsevier B.V. All rights reserved.