HVJ脂质体介导的基因体内转导入肝细胞。

HVJ-liposome mediated gene transfer into hepatocytes in vivo.

作者信息

Hirano T, Fujimoto J, Ueki T, Yamamoto H, Takeuchi M, Okamoto E, Takahashi H, Morisita R, Sawa Y, Kaneda Y

机构信息

First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan.

出版信息

J Hepatol. 1998 Dec;29(6):910-4. doi: 10.1016/s0168-8278(98)80118-9.

DOI:10.1016/s0168-8278(98)80118-9

PMID:9875637

Abstract

BACKGROUND/AIMS: The efficient transduction of appropriate target cells will be critical for gene therapy. We evaluated the suitability of hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer for gene therapy of liver diseases.

METHODS

The Escherichia coli beta-galactosidase (beta-gal) gene was introduced into rat liver by HVJ-liposome to examine gene transfer efficacy and persistence of expression with or without partial hepatectomy prior to transfection.

RESULTS

About 30% of hepatocytes were transduced after portal vein injection. Gene expression was transient, with only 2% of hepatocytes expressing beta-gal after 4 weeks. However, partial hepatectomy performed 24 h prior to injection resulted in persistently high levels of beta-gal for 4 weeks after injection. A 247-bp beta-gal polymerase chain reaction fragment transcript was detected in livers of transfected rats, but not in livers of control rats. The rat livers following gene transfer were histologically normal, and serum glutamic-pyruvic transaminase was not found to be elevated in rats.

CONCLUSIONS

Our results demonstrate that HVJ-liposome-mediated gene transfer produced high gene transduction and persistent gene expression in the liver.

摘要

背景/目的：高效转导合适的靶细胞对于基因治疗至关重要。我们评估了日本血凝病毒（HVJ）-脂质体介导的基因转移在肝脏疾病基因治疗中的适用性。

方法

通过HVJ-脂质体将大肠杆菌β-半乳糖苷酶（β-gal）基因导入大鼠肝脏，以检测在转染前有无部分肝切除的情况下基因转移效率和表达持续性。

结果

门静脉注射后约30%的肝细胞被转导。基因表达是短暂的，注射4周后只有2%的肝细胞表达β-gal。然而，注射前24小时进行部分肝切除导致注射后4周β-gal水平持续较高。在转染大鼠的肝脏中检测到247bp的β-gal聚合酶链反应片段转录本，但在对照大鼠的肝脏中未检测到。基因转移后的大鼠肝脏在组织学上正常，且未发现大鼠血清谷丙转氨酶升高。