Successful gene transfer using adeno-associated virus vectors into the kidney: Comparison among adeno-associated virus serotype 1-5 vectors in vitro and in vivo
Successful gene transfer using adeno-associated virus vectors into the kidney: Comparison among adeno-associated virus serotype 1-5 vectors in vitro and in vivo
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DOI：
10.1159/000077378
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发表时间：
2004-04-01
影响因子：
--
通讯作者：
Kusano, E
中科院分区：
文献类型：
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作者：
Takeda, S;Takahashi, M;Kusano, E
背景/目的：基因转移到肾脏作为一种新的治疗方法有很大的潜力。然而，尚未建立将基因转移到肾脏中的有效方法。我们探讨了肾细胞在体外和体内使用腺相关病毒（AAV）血清型1 - 5载体编码的β-半乳糖苷酶基因的转导效率。方法：体外实验中，将AAV血清型衍生载体转染大鼠肾上皮细胞系NRK 52 E细胞。在体内研究中，使用基于导管的基因递送系统在大鼠和小鼠中模拟临床程序将AAV血清型衍生的载体选择性地注射到肾脏中。根据β-半乳糖苷酶的表达，对基因表达的效率进行组织学评价。结果如下：AAV血清型1、2和5载体在体外转导大鼠肾上皮细胞系NRK 52 E细胞，而AAV血清型3或4载体显示无转导。此外，肾脏特异性注射AAV血清型2载体在体内成功地在肾小管上皮细胞中转导，但不在肾小球、血管或间质细胞中转导，而其余血清型显示无转导。结论：由于肾特异性基因通过肾动脉导管输送是高度可行的，在人类，这些发现提供了有用的信息，有前途的策略，在肾基因治疗。版权所有（C）2004 S. Karger AG，巴塞尔。
Background/Aim: Gene transfer into the kidney has great potential as a novel therapeutic approach. However, an efficient method of gene transfer into the kidney has not been established. We explored the transduction efficiency of renal cells in vitro and in vivo using adeno-associated virus (AAV) serotype 1 - 5 vectors encoding the - galactosidase gene. Methods: In the in vitro study, rat kidney epithelial cell line NRK52E cells were transfected with AAV serotype derived vectors. In the in vivo study, AAV serotype derived vectors were selectively injected into the kidney using a catheter-based gene delivery system in rats and mice mimicking the clinical procedure. The efficiency of gene expression was histologically evaluated on the basis of the beta-galactosidase expression. Results: AAV serotype 1, 2, and 5 vectors transduced in rat kidney epithelial cell line NRK52E cells in vitro, whereas AAV serotype 3 or 4 vectors showed no transduction. In addition, the kidney-specific injection of AAV serotype 2 vectors successfully transduced in tubular epithelial cells, but not in glomerular, blood vessel, or interstitial cells in vivo, whereas the rest of the serotypes showed no transduction. Conclusion: Since kidney-specific gene delivery via the renal artery by catheterization is highly feasible in humans, these findings provide useful information for promising strategies in renal gene therapy. Copyright (C) 2004 S. Karger AG, Basel.