Ex vivo hepatic gene transfer in mouse using a defective herpes simplex virus‐1 vector-猫眼课题宝

使用有缺陷的单纯疱疹病毒-1载体进行小鼠离体肝基因转移

DOI：

10.1002/hep.1840210324

发表时间：

1995

期刊：

Hepatology

影响因子：

13.5

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

B. Lu;Sanjeev Gupta;H. Federoff

A defective amplicon herpes simplex virus‐1 (HSV‐1) vector, HSVlac, was used to transfer an E. coli lacZ reporter gene into primary hepatocytes. The lacZ gene was driven by the HSV immediate early (IE) 4/5 promoter. Use of the HSVlac vector resulted in highly efficient gene transfer. Because difficulties in culturing primary hepatocytes impose limitations in ex vivo gene therapy, we sought to determine whether use of the HSVlac vector could simplify gene transfer. Therefore, we incubated HSVlac with primary hepatocytes in suspension and found that the lacZ gene was still transferred with great rapidity and efficiency. To examine lacZ expression in transduced hepatocytes in vivo, we used a mouse hepatocyte transplantation system. In congeneic recipients of primary hepatocytes transduced with HSVlac in suspension, the lacZ gene was expressed in liver and spleen up to 2 weeks. However, survival of transplanted hepatocytes, as well as persistence of HSVlac genome in recipient organs, was demonstrated for up to an 11‐week duration of the experiment. These findings suggest that in vivo regulation of the HSV IE4/5 promoter was responsible for the short‐term expression of lacZ, which should be overcome by the use of liver‐specific promoters. Therefore, our results indicate the feasibility of hepatic gene transfer with a defective HSV‐1 vector.