Efficient gene transfer to rat renal glomeruli with recombinant adenoviral vectors.
Efficient gene transfer to rat renal glomeruli with recombinant adenoviral vectors.
复制标题
用重组腺病毒载体将基因有效转移至大鼠肾小球。
DOI：
10.1089/104303401750061203
复制
发表时间：
2001
影响因子：
4.2
通讯作者：
Ray,PE
中科院分区：
文献类型：
--
作者：
Ye,X;Liu,X;Li,Z;Ray,PE
重组腺病毒是肾基因转移的有吸引力的载体，因为它们可以有效地转导非分裂细胞。然而，尽管事实上肾小球很容易通过肾循环进入，但使用腺病毒载体将外源基因特异性递送到肾小球的尝试在啮齿类动物中取得的成功有限。发现简单地将腺病毒载体动脉内注射到肾循环中或将病毒与肾脏一起孵育较长时间不足以达到此目的。在这项研究中，我们建立了一种有效的基因转移方案，使用腺病毒载体在大鼠肾小球细胞中表达外源基因。我们首次证明，通过将重组腺病毒（Ad.CBlacZ）缓慢注入右肾动脉15分钟，可以有效转导大鼠肾小球内皮细胞。在肾小球中实现了高水平的lacZ表达，而不对肾小球或其他肾脏结构造成显着损伤。病毒介导的表达持续至少21天。这些数据证明了使用重组腺病毒载体作为工具来研究外源基因表达对体内大鼠肾小球结构和功能的影响的可行性。
Recombinant adenoviruses are attractive vectors for renal gene transfer since they can efficiently transduce nondividing cells. However, despite the fact that renal glomeruli are easily accessible via the renal circulation, attempts to deliver foreign genes specifically into renal glomeruli, using adenoviral vectors, have had limited success in rodents. A simple intraarterial injection of adenoviral vectors into the renal circulation or incubation of the virus with the kidney for an extended period of time was found to be insufficient for this purpose. In this study, we have established an efficient gene transfer protocol to express foreign genes in rat renal glomerular cells, using adenoviral vectors. We demonstrated, for the first time, that rat glomerular endothelial cells could be efficiently transduced by slowly infusing a recombinant adenovirus (Ad.CBlacZ) into the right renal artery for a period of 15 min. High levels oflacZexpression were achieved in renal glomeruli without causing significant damage to renal glomeruli or other kidney structures. The virus-mediated expression lasted for at least 21 days. These data demonstrate the feasibility of using recombinant adenoviral vectors as a tool with which to study the effect of foreign gene expression on the structure and function of rat renal glomeruliin vivo.