Efficient retroviral gene transfer to the liver in vivo using nonpolypeptidic mitogens
Efficient retroviral gene transfer to the liver in vivo using nonpolypeptidic mitogens
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DOI：
10.1006/bbrc.2001.5495
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发表时间：
2001-09-07
影响因子：
3.1
通讯作者：
Ferry, N
中科院分区：
文献类型：
--
作者：
Pichard, V;Aubert, D;Ferry, N
重组逆转录病毒载体是实现治疗基因在肝脏中持续表达的有吸引力的工具。然而，这些载体的有效转导需要细胞分裂。在这里，我们报告，两个广泛使用的肝有丝分裂原，三碘甲状腺原氨酸（T3）和醋酸环丙孕酮（CPA），使肝细胞转导与重组逆转录病毒载体在体内输送到血液中。单独或联合使用T3和CPA治疗，导致肝细胞复制主要在门脉道周围增加。促有丝分裂活性使得在相同位置培养肝细胞成为可能。此外，当一起给药时，两种药物协同作用，转导水平达到5%的肝细胞。这种转导水平与许多遗传性肝病的临床应用相容。由于这两种化合物具有长期的安全临床使用历史，我们建议这些肝有丝分裂原可能具有潜在的肝定向基因治疗的临床应用。(C)北京：科学出版社.
Recombinant retroviral vectors are attractive tools for achieving sustained expression of a therapeutic gene in the liver. However, cell division is required for efficient transduction with these vectors. Here we report that two widely used liver mitogens, triiodothyronin (T3) and cyproterone acetate (CPA), enable hepatocyte transduction with recombinant retroviral vectors delivered in vivo into the bloodstream. Treatment with T3 as well as CPA, alone or in combination, resulted in an increase in hepatocyte replication predominantly around the portal tract. The mitogenic activity made it possible to transduce hepatocytes in the same location. Moreover, when administered together, the two drugs synergized and the transduction level reached 5% of hepatocytes. This transduction level is compatible with clinical applications for a number of inherited liver diseases. Since these two compounds have a long history of safe clinical use, we propose that these liver mitogens may have potential for clinical application in liver-directed gene therapy. (C) 2001 Academic Press.