Moullier P, Friedlander G, Calise D, Ronco P, Perricaudet M, Ferry N
Département SIDA-Rétrovirus, Institut Pasteur, Paris, France.
Kidney Int. 1994 Apr;45(4):1220-5. doi: 10.1038/ki.1994.162.
The efficient introduction of genetic material into quiescent renal cells is potentially important in the study of renal physiopathology and for gene therapy of kidney related disorders. A replication-deficient adenoviral vector that contained a reporter gene encoding the nuclear beta-galactosidase was either selectively perfused into the renal artery or infused through a retrograde catheter into the pyelic cavity of the left kidney of adult rats. Highly efficient gene transfer was achieved by either route of administration, and nuclear beta-galactosidase activity was detected for two to four weeks following a progressive decline of expression. Genetically-modified cells were identified as proximal tubular cells when the adenoviral vector was selectively perfused via the renal artery, while tubular cells from the papilla and medulla were selectively transduced by retrograde infusion of the viral vector. No obvious cytopathic effect was observed. We conclude that: (i) efficient gene transfer in renal tubular cells can be achieved by adenoviral vectors; (ii) the targeted cell population can be chosen through the route of administration.
将遗传物质有效导入静止的肾细胞，在肾脏生理病理学研究以及肾脏相关疾病的基因治疗中可能具有重要意义。一种携带编码核β-半乳糖苷酶报告基因的复制缺陷型腺病毒载体，通过选择性灌注到肾动脉或经逆行导管注入成年大鼠左肾肾盂腔内。通过这两种给药途径均实现了高效的基因转移，并且在表达逐渐下降后，核β-半乳糖苷酶活性可检测到两到四周。当腺病毒载体通过肾动脉选择性灌注时，基因修饰的细胞被鉴定为近端肾小管细胞，而通过逆行注入病毒载体可选择性转导乳头和髓质的肾小管细胞。未观察到明显的细胞病变效应。我们得出结论：（i）腺病毒载体可在肾小管细胞中实现高效基因转移；（ii）可通过给药途径选择靶向细胞群体。
