Effective Gene Transfer into Central Nervous System Following聽Ultrasound-Microbubbles-Induced Opening of the聽Blood-Brain Barrier

详细信息	查看全文 | 推荐本文 |

• 作者：Qin Huang^&lowast ; ; ^&dagger ; ; Jinmu Deng^&lowast ; ; Zongyi Xie^&lowast ; ; Feng Wang^&lowast ; ; Song Chen^&lowast ; ; Bo Lei^&lowast ; ; Peng Liao^&lowast ; ; Ning Huang^&lowast ; ; Zhibiao Wang^&dagger ; ; Zhigang Wang^&Dagger ; ; Yuan Cheng^&lowast ; ; ^{chengyuan023@yahoo.com.cn}
• 关键词：Blood-brain barrier ; Central nervous system ; Gene therapy ; Ultrasound ; Microbubbles
• 刊名：Ultrasound in Medicine and Biology
• 出版年：2012
• 期刊代码：82_03015629
• 类别：ph
• 出版时间：July, 2012
• 卷：38
• 期：7
• 页码：1234-1243
• 文件大小：1001 K

摘要

To investigate whether ultrasound-targeted microbubble destruction (UTMD) could transfer gene into central nervous system (CNS) following blood-brain barrier disruption (BBBD), DNA-loaded microbubbles were infused into the mice intravenously following ultrasonic exposure. Opening of the BBB, changes of mRNA and expression of enhanced green fluorescent protein (EGFP), and safety evaluation were measured. By UTMD, EGFP were substantially expressed in the cytoplasm of the neurons at the sonicated area with minor erythrocytes extravasation and the mRNA and expression of EGFP were markedly enhanced by about 15-fold and 10-fold, respectively, than that with US alone (p < 0.01). No EGFP was detected in the mice treated with DNA-loaded microbubbles or plasmid alone. The gene expression reached a climax at 48 h, gradually reduced to a much lower level thereafter. These results demonstrated UTMD could effectively enhance exogenous gene delivery and expression in CNS following BBBD, and聽this technique may provide a new method for CNS gene therapy.