FACTORS INFLUENCING RETROVIRAL-MEDIATED GENE-TRANSFER INTO HEPATOCYTES IN-VIVO
FACTORS INFLUENCING RETROVIRAL-MEDIATED GENE-TRANSFER INTO HEPATOCYTES IN-VIVO
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DOI：
10.1089/hum.1994.5.7-803
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发表时间：
1994-07-01
影响因子：
4.2
通讯作者：
FERRY, N
中科院分区：
文献类型：
--
作者：
BRANCHEREAU, S;CALISE, D;FERRY, N
直接基因转移到肝细胞是一个有吸引力的替代器官移植治疗遗传性肝病。这种方法受到难以获得、培养和再植入肝细胞或转基因表达稳定性差的阻碍。在本报告中，我们表明，直接在体内感染肝细胞与逆转录病毒载体后，部分肝切除导致终身表达的转基因在成年大鼠和小鼠。我们证明了肝细胞对感染易感性的动力学与细胞分裂的动力学密切相关。我们还提出的证据表明，一个完整的血管排斥的器官允许更好的基因转移相比，简单的门静脉输液的病毒颗粒，大概是通过一个更高的体积的逆转录病毒的介质输送到肝脏。
Direct gene transfer into hepatocytes represents an attractive alternative to organ transplantation for the treatment of genetic liver diseases. This approach is hampered either by the difficulty to obtain, cultivate, and reimplant hepatocytes or by the poor stability of the expression of the transgene. In the present report, we show that direct in vivo infection of hepatocytes with a retroviral vector following partial hepatectomy results in a life-long expression of the transgene in adult rats and mice. We demonstrate that the kinetics of hepatocyte susceptibility to infection is closely associated with the kinetics of cell division. We also present evidence that a complete vascular exclusion of the organ allows better gene transfer as compared to simple portal infusion of the viral particles, presumably through a higher volume of retrovirus-containing medium delivered to the liver.