GENE-EXPRESSION FOLLOWING DIRECT-INJECTION OF DNA INTO LIVER

被引:217
作者
HICKMAN, MA
MALONE, RW
LEHMANNBRUINSMA, K
SIH, TR
KNOELL, D
SZOKA, FC
WALZEM, R
CARLSON, DM
POWELL, JS
机构
[1] UNIV CALIF DAVIS,DEPT MED PATHOL,GENE THERAPY PROGRAM,DAVIS,CA 95616
[2] UNIV CALIF DAVIS,DEPT MED HEMATOL & ONCOL,DAVIS,CA 95616
[3] UNIV CALIF DAVIS,DEPT VET MED MOLEC BIOSCI,DAVIS,CA 95616
[4] UNIV CALIF SAN FRANCISCO,DEPT PHARM & PHARMACEUT CHEM,SAN FRANCISCO,CA 94143
关键词
D O I
10.1089/hum.1994.5.12-1477
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The liver is an attractive target tissue for gene therapy, Current approaches for hepatic gene delivery include retroviral and adenoviral vectors, liposome/DNA, and peptide/DNA complexes, This study describes a technique for direct injection of DNA into liver that led to significant gene expression, Gene expression was characterized in both rats and cats following injection of plasmid DNA encoding several different proteins, Luciferase activity was measured after injection of plasmid DNA encoding the luciferase gene (pCMVL), beta-galactosidase (beta-Gal) activity was evaluated in situ using plasmid DNA encoding Lac Z (pCMV beta), and serum concentration of secreted human alpha-1-antitrypsin was measured following injection of plasmid DNA encoding this protein (pRC/CMV-sHAT), Several variables, including injection technique, DNA dose, and DNA diluent, were investigated, Direct injection of pCMVL resulted in maximal luciferase expression at 24-48 hr. beta-Gal staining demonstrated that the majority of transfected hepatocytes were located near the injection site. Significant concentrations of human alpha-1-antitrypsin were detected in the serum of animals injected with pRC/CMV-sHAT, These findings demonstrate the general principle that direct injection of plasmid DNA into liver can lead to significant gene expression.
引用
收藏
页码:1477 / 1483
页数:7
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