腺相关病毒载体介导的转基因整合到神经元和其他非分裂细胞靶点中。
Adeno-associated virus vector-mediated transgene integration into neurons and other nondividing cell targets.
作者信息
Wu P, Phillips M I, Bui J, Terwilliger E F
机构信息
Divisions of Experimental Medicine and Hematology/Oncology, Beth Israel Deaconess Medical Center and Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.
出版信息
J Virol. 1998 Jul;72(7):5919-26. doi: 10.1128/JVI.72.7.5919-5926.1998.
Abstract
The site-specific integration of wild-type adeno-associated virus (wtAAV) into the human genome is a very attractive feature for the development of AAV-based gene therapy vectors. However, knowledge about integration of wtAAV, as well as currently configured recombinant AAV (rAAV) vectors, is limited. By using a modified Alu-PCR technique to amplify and sequence the vector-cellular junctions, we provide the first direct evidence both in vitro and in vivo of rAAV-mediated transgene integration in several types of nondividing cells, including neurons. This novel technique will be highly useful for further delineating the mechanisms underlying AAV-mediated integration, including issues of frequency, site preference, and DNA rearrangement in human as well as animal cells. Results from these studies should be beneficial for the development of the next generation of gene delivery vectors.
摘要
野生型腺相关病毒（wtAAV）位点特异性整合到人类基因组中，这对于基于AAV的基因治疗载体的开发而言是一个极具吸引力的特性。然而，关于wtAAV以及当前构建的重组AAV（rAAV）载体的整合情况，我们所知有限。通过使用改良的Alu-PCR技术扩增并对载体-细胞连接点进行测序，我们首次在体外和体内提供了rAAV介导的转基因在包括神经元在内的多种非分裂细胞中整合的直接证据。这项新技术对于进一步阐明AAV介导整合的潜在机制将非常有用，这些机制包括人类及动物细胞中的整合频率、位点偏好和DNA重排等问题。这些研究结果应有助于下一代基因递送载体的开发。
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