PERSISTENT GENE-EXPRESSION AFTER RETROVIRAL GENE-TRANSFER INTO LIVER-CELLS INVIVO

被引:116
作者
KALEKO, M [1 ]
GARCIA, JV [1 ]
MILLER, AD [1 ]
机构
[1] FRED HUTCHINSON CANC RES CTR,PROGRAM MOLEC MED,SEATTLE,WA 98104
关键词
D O I
10.1089/hum.1991.2.1-27
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 development of liver-directed gene therapy protocols depends upon the ability to transfer genes into a large number of liver cells such that the genes are expressed persistently. We used a retroviral vector to transfer the gene for neomycin phosphotransferase (neo) into mouse liver cells in vivo. Direct injection of the retrovirus preparation into mitotically active (regenerating) liver parenchyma resulted in efficient gene transfer, with neo sequences detectable in the livers of every animal tested 10 weeks to 6 months later. The neo gene was expressed for at least 3 months. This methodology may eventually be applicable to the treatment of human disease.
引用
收藏
页码:27 / 32
页数:6
相关论文
共 24 条
[1]   DIRECT INTRODUCTION OF GENES INTO RATS AND EXPRESSION OF THE GENES [J].
BENVENISTY, N ;
RESHEF, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (24) :9551-9555
[2]   DIRECT TRANSFECTION OF VIRAL AND PLASMID DNA INTO THE LIVER OR SPLEEN OF MICE [J].
DUBENSKY, TW ;
CAMPBELL, BA ;
VILLARREAL, LP .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (23) :7529-7533
[3]  
FRIEDMANN T, 1989, MOL BIOL MED, V6, P117
[4]  
HATZOGLOU M, 1990, J BIOL CHEM, V265, P17285
[5]   MOLONEY LEUKEMIA-VIRUS GENE-EXPRESSION AND GENE AMPLIFICATION IN PRELEUKEMIC AND LEUKEMIC BALB-MO MICE [J].
JAENISCH, R .
VIROLOGY, 1979, 93 (01) :80-90
[6]   TREATMENT OF MICE WITH 5-AZACYTIDINE EFFICIENTLY ACTIVATES SILENT RETROVIRAL GENOMES IN DIFFERENT TISSUES [J].
JAENISCH, R ;
SCHNIEKE, A ;
HARBERS, K .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1985, 82 (05) :1451-1455
[7]   DENOVO METHYLATION AND EXPRESSION OF RETROVIRAL GENOMES DURING MOUSE EMBRYOGENESIS [J].
JAHNER, D ;
STUHLMANN, H ;
STEWART, CL ;
HARBERS, K ;
LOHLER, J ;
SIMON, I ;
JAENISCH, R .
NATURE, 1982, 298 (5875) :623-628
[8]   INCREASED EXPRESSION OF DNA COINTRODUCED WITH NUCLEAR-PROTEIN IN ADULT-RAT LIVER [J].
KANEDA, Y ;
IWAI, K ;
UCHIDA, T .
SCIENCE, 1989, 243 (4889) :375-378
[9]  
KANEDA Y, 1989, J BIOL CHEM, V264, P12126
[10]   RETROVIRAL GENE-TRANSFER INTO PRIMARY HEPATOCYTES - IMPLICATIONS FOR GENETIC THERAPY OF LIVER-SPECIFIC FUNCTIONS [J].
LEDLEY, FD ;
DARLINGTON, GJ ;
HAHN, T ;
WOO, SLC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (15) :5335-5339