Max von Pettenkofer-Institut, Department of Virology, Ludwig-Maximilians-Universität Munich, Pettenkoferstr. 9A, 80336 Munich, Germany.
Viruses. 2009 Dec;1(3):1295-324. doi: 10.3390/v1031295. Epub 2009 Dec 15.
The turbulent history of clinical trials in viral gene therapy has taught us important lessons about vector design and safety issues. Much effort was spent on analyzing genotoxicity after somatic integration of therapeutic DNA into the host genome. Based on these findings major improvements in vector design including the development of viral hybrid vectors for somatic integration have been achieved. This review provides a state-of-the-art overview of available hybrid vectors utilizing viruses for high transduction efficiencies in concert with various integration machineries for random and targeted integration patterns. It discusses advantages but also limitations of each vector system.
病毒基因治疗临床试验的曲折历史,让我们了解到载体设计和安全问题的重要教训。人们花费了大量精力分析治疗性 DNA 整合到宿主基因组后的遗传毒性。基于这些发现,载体设计得到了重大改进,包括开发用于体细胞整合的病毒杂交载体。本文综述了目前可用的杂交载体,这些载体利用病毒实现高效转导,同时结合各种随机和靶向整合机制,讨论了每种载体系统的优势和局限性。