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本文引用的文献

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Adeno-associated virus vector integration junctions.腺相关病毒载体整合连接点。
J Virol. 1997 Nov;71(11):8429-36. doi: 10.1128/JVI.71.11.8429-8436.1997.
2
Encapsidation of adeno-associated virus type 2 Rep proteins in wild-type and recombinant progeny virions: Rep-mediated growth inhibition of primary human cells.野生型和重组子代病毒粒子中2型腺相关病毒Rep蛋白的衣壳化：Rep介导的原代人类细胞生长抑制
J Virol. 1997 Oct;71(10):7361-71. doi: 10.1128/JVI.71.10.7361-7371.1997.
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Structural and functional heterogeneity of integrated recombinant AAV genomes.整合的重组腺相关病毒基因组的结构和功能异质性。
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Potent inhibition of human immunodeficiency virus type 1 in primary T cells and alveolar macrophages by a combination anti-Rev strategy delivered in an adeno-associated virus vector.通过腺相关病毒载体传递的联合抗Rev策略对原代T细胞和肺泡巨噬细胞中1型人类免疫缺陷病毒的强效抑制作用。
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Efficient transduction of green fluorescent protein in spinal cord neurons using adeno-associated virus vectors containing cell type-specific promoters.使用含有细胞类型特异性启动子的腺相关病毒载体高效转导脊髓神经元中的绿色荧光蛋白。
Gene Ther. 1997 Jan;4(1):16-24. doi: 10.1038/sj.gt.3300358.
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Site-specific integration by adeno-associated virus: a basis for a potential gene therapy vector.
Gene Ther. 1997 Jan;4(1):4-5. doi: 10.1038/sj.gt.3300357.
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Adeno-associated virus Rep78 protein and terminal repeats enhance integration of DNA sequences into the cellular genome.腺相关病毒Rep78蛋白和末端重复序列增强DNA序列整合到细胞基因组中。
J Virol. 1997 Apr;71(4):3299-306. doi: 10.1128/JVI.71.4.3299-3306.1997.
8
Recombinant adeno-associated virus for muscle directed gene therapy.用于肌肉定向基因治疗的重组腺相关病毒
Nat Med. 1997 Mar;3(3):306-12. doi: 10.1038/nm0397-306.
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Lack of site-specific integration of the recombinant adeno-associated virus 2 genomes in human cells.重组腺相关病毒2基因组在人类细胞中缺乏位点特异性整合。
Hum Gene Ther. 1997 Feb 10;8(3):275-84. doi: 10.1089/hum.1997.8.3-275.
10
Prolonged reduction of high blood pressure with an in vivo, nonpathogenic, adeno-associated viral vector delivery of AT1-R mRNA antisense.使用体内非致病性腺相关病毒载体递送AT1-R mRNA反义核酸对高血压进行长期降压治疗。
Hypertension. 1997 Jan;29(1 Pt 2):374-80. doi: 10.1161/01.hyp.29.1.374.

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.

DOI:10.1128/JVI.72.7.5919-5926.1998
PMID:9621054
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC110396/
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。