腺相关病毒作为肝脏定向基因治疗的载体。
Adeno-associated virus as a vector for liver-directed gene therapy.
作者信息
Xiao W, Berta S C, Lu M M, Moscioni A D, Tazelaar J, Wilson J M
机构信息
Institute for Human Gene Therapy and Departments of Molecular and Cellular Engineering and of Medicine, University of Pennsylvania, and the Wistar Institute, Philadelphia, Pennsylvania, USA.
出版信息
J Virol. 1998 Dec;72(12):10222-6. doi: 10.1128/JVI.72.12.10222-10226.1998.
Abstract
Factors relevant to the successful application of adeno-associated virus (AAV) vectors for liver-directed gene therapy were evaluated. Vectors with different promoters driving expression of human alpha-1-antitrypsin (alpha-1AT) were injected into the portal circulation of immunodeficient mice. alpha-1AT expression was stable but dependent on the promoter. Southern analysis of liver DNA revealed approximately 0.1 to 2.0 provirus copies/diploid genome in presumed head-to-tail concatamers. In situ hybridization and immunohistochemical analysis revealed expression in approximately 5% of hepatocytes clustered in the pericentral region. These results support the use of AAV as a vector for diseases treatable by targeting of hepatocytes.
摘要
评估了与腺相关病毒（AAV）载体成功应用于肝脏定向基因治疗相关的因素。将驱动人α-1抗胰蛋白酶（α-1AT）表达的不同启动子的载体注入免疫缺陷小鼠的门静脉循环。α-1AT表达稳定，但依赖于启动子。肝脏DNA的Southern分析显示，在假定的头对头串联体中，每二倍体基因组约有0.1至2.0个前病毒拷贝。原位杂交和免疫组织化学分析显示，在中央周围区域聚集的约5%的肝细胞中有表达。这些结果支持将AAV用作靶向肝细胞可治疗疾病的载体。
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本文引用的文献
1
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J Virol. 1998 May;72(5):4212-23. doi: 10.1128/JVI.72.5.4212-4223.1998.
2
Real-time, noninvasive in vivo assessment of adeno-associated virus-mediated retinal transduction.腺相关病毒介导的视网膜转导的实时、无创体内评估。
Invest Ophthalmol Vis Sci. 1997 Dec;38(13):2857-63.
3
Persistent and therapeutic concentrations of human factor IX in mice after hepatic gene transfer of recombinant AAV vectors.重组腺相关病毒载体肝基因转移后小鼠体内人凝血因子IX的持续治疗浓度
Nat Genet. 1997 Jul;16(3):270-6. doi: 10.1038/ng0797-270.
4
Efficient photoreceptor-targeted gene expression in vivo by recombinant adeno-associated virus.重组腺相关病毒在体内实现高效的光感受器靶向基因表达。
Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6916-21. doi: 10.1073/pnas.94.13.6916.
5
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Gene. 1997 Apr 29;190(1):203-10. doi: 10.1016/s0378-1119(96)00576-8.
6
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.
7
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Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1426-31. doi: 10.1073/pnas.94.4.1426.
8
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Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14082-7. doi: 10.1073/pnas.93.24.14082.
9
Efficient long-term gene transfer into muscle tissue of immunocompetent mice by adeno-associated virus vector.腺相关病毒载体将基因高效长期转移至免疫活性小鼠的肌肉组织
J Virol. 1996 Nov;70(11):8098-108. doi: 10.1128/JVI.70.11.8098-8108.1996.
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