Max von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University Munich, Pettenkofer Strasse 9a, Munich, Germany. .
Curr Gene Ther. 2011 Oct;11(5):363-74. doi: 10.2174/156652311797415890.
The Sleeping Beauty (SB) transposase system for somatic integration offers great potential for in vivo gene therapeutic applications and genome engineering. Until recently, however, efficacy of SB transposase as a gene transfer vector especially in large animals was lacking. Herein, we report about the newest viral vector development for delivery of the SB transposase system into large mammals. Over the past decade various hyperactive versions of SB transposase and advanced adenovirus vectors enabling efficient and safe delivery of transgenes in vivo were developed. Already several years ago it was demonstrated that adenovirus vectors can be used for delivery of the SB transposase system into murine liver. Our newest study showed for the first time that a hyperactive transposase system delivered by high-capacity adenoviral vectors can result in somatic integration of exogenous DNA in canine liver, facilitating stabilized transgene expression and phenotypic correction for up to three years in a canine model of human disease. In this review we discuss safety issues and further improvements of this adenovirus based hybrid vector system for somatic integration. In the future this approach paves new paths towards the possible cure of human genetic diseases and novel strategies for in vivo genome engineering in large mammals.
睡眠美人（SB）转座酶系统用于体细胞核移植具有很大的应用潜力，可用于体内基因治疗和基因组工程。然而，直到最近，SB 转座酶作为基因转移载体的功效，尤其是在大型动物中，仍然缺乏。本文介绍了最新的病毒载体开发，用于将 SB 转座酶系统递送至大型哺乳动物。在过去的十年中，已经开发出了多种超活型 SB 转座酶和先进的腺病毒载体，能够在体内高效、安全地传递转基因。几年前，已经证明腺病毒载体可用于将 SB 转座酶系统递送至小鼠肝脏。我们的最新研究首次表明，高容量腺病毒载体传递的超活转座酶系统可导致犬肝脏中外源 DNA 的体细胞整合，从而实现长达三年的稳定转基因表达和表型校正，在人类疾病的犬模型中。在本文中，我们讨论了这个基于腺病毒的杂交载体系统的安全性问题和进一步的改进，用于体细胞核移植。将来，这种方法为人类遗传性疾病的可能治愈和大型哺乳动物体内基因组工程的新策略铺平了道路。
