Viral Hybrid Vectors for Somatic Integration - Are They the Better Solution 英文参考文献.docVIP

Viruses 2009, 1, 1295-1324; doi:10.3390/v1031295 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Viral Hybrid Vectors for Somatic Integration - Are They the Better Solution? Nadine Müther, Nadja Noske and Anja Ehrhardt * Max von Pettenkofer-Institut, Department of Virology, Ludwig-Maximilians-Universit?t Munich, Pettenkoferstr. 9A, 80336 Munich, Germany * Author to whom correspondence should be addressed; E-Mail: ehrhardt@mvp.uni-muenchen.de; Tel.: +49 89 5160 5270; Fax: + 49 89 5160 5292. Received: 30 September 2009; in revised form: 4 December 2009 / Accepted: 10 December 2009 / Published: 15 December 2009 Abstract: 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. Keywords: hybrid vector; somatic integration; adenovirus; retrovirus; adeno-associated virus; herpes simplex virus; targeted integration; Sleeping Beauty transposase; PhiC31 integrase; zinc-finger nuclease 1. Introduction The development of novel and safer vector tools for stable maintenance of therapeutic DNA and transgene products within a cell, especially in rapidly dividing cells (e.g., bone marrow derived cells), is of great interest to the research community. For instance therapies for these genetic diseases would benefit from such tools because they