Silcox Christina E, Smith Roy C, King Randy, McDannold Nathan, Bromley Peter, Walsh Kenneth, Hynynen Kullervo
Brigham & Women's Hospital/Harvard Medical School, Boston, MA 02115, USA.
Ultrasound Med Biol. 2005 Jul;31(7):965-70. doi: 10.1016/j.ultrasmedbio.2005.03.009.
The need for efficient and controlled delivery is one of the major obstacles to clinical use of gene therapy. In this study, we investigated the use of magnetic resonance imaging-monitored ultrasound (US) to induce expression of luciferase after local injection of the construct Ad-HSP-Luc, an adenoviral vector containing a transgene encoding firefly luciferase under the control of the human hsp70B promoter. The hsp promoter allows induction of the associated transgene only in areas that are subsequently heated after infection. US imaging was used to guide the injection of purified virus into both lobes of the prostates of three beagles. At 48 h after injection, the left lobe of the prostate was heated using a 1.5-MHz US transducer driven by a multichannel radiofrequency system and employing an magnetic resonance imaging guidance system. High levels of luciferase expression were observed only in areas exposed to ultrasonic heating. This study demonstrates the feasibility of using ultrasonic heating to control transgene expression spatially using a minimally-invasive approach.
高效且可控的递送需求是基因治疗临床应用的主要障碍之一。在本研究中，我们研究了在局部注射构建体Ad-HSP-Luc（一种腺病毒载体，其包含在人hsp70B启动子控制下编码萤火虫荧光素酶的转基因）后，利用磁共振成像监测的超声（US）诱导荧光素酶表达的情况。hsp启动子仅允许在感染后随后被加热的区域诱导相关转基因。超声成像用于引导将纯化病毒注射到三只比格犬前列腺的两个叶中。注射后48小时，使用由多通道射频系统驱动并采用磁共振成像引导系统的1.5MHz超声换能器对前列腺左叶进行加热。仅在暴露于超声加热的区域观察到高水平的荧光素酶表达。本研究证明了使用超声加热以微创方法在空间上控制转基因表达的可行性。
