LONG-TERM INVIVO EXPRESSION OF RETROVIRUS-MEDIATED GENE-TRANSFER IN MOUSE FIBROBLAST IMPLANTS

被引:269
作者
SCHARFMANN, R
AXELROD, JH
VERMA, IM
机构
[1] Molec. Biol. and Virology Laboratory, Salk Institute, San Diego, CA 92186-5800
[2] Department of Biological Chemistry, Institute of Life Sciences, Hebrew University
关键词
VECTORS; FACTOR-IX; BETA-GALACTOSIDASE; PROMOTERS; COLLAGEN IMPLANTS;
D O I
10.1073/pnas.88.11.4626
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Toward the goal of gene therapy, we have been attempting to establish model somatic cell systems with the potential of sustained expression of the foreign gene. We report here that long-term expression of foreign genes in mouse embryo fibroblast implants can be achieved if a housekeeping gene promoter is used to drive transcription. Specifically, we have shown that in implants containing a beta-galactosidase gene linked to either an immediate early promoter of cytomegalo-virus or a dihydrofolate reductase (DHFR) gene promoter, only the DHFR promoter allows long-term expression. We propose that choice of the promoter manifests significant influence on the long-term expression of genes introduced in fibroblast implants by retroviral vectors.
引用
收藏
页码:4626 / 4630
页数:5
相关论文
共 22 条
[1]   PHENOTYPIC CORRECTION OF FACTOR-IX DEFICIENCY IN SKIN FIBROBLASTS OF HEMOPHILIC DOGS [J].
AXELROD, JH ;
READ, MS ;
BRINKHOUS, KM ;
VERMA, IM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (13) :5173-5177
[2]  
BELL S, 1983, J INVEST DERMATOL, V81, P25
[3]   EVIDENCE THAT THE PACKAGING SIGNAL OF MOLONEY MURINE LEUKEMIA-VIRUS EXTENDS INTO THE GAG REGION [J].
BENDER, MA ;
PALMER, TD ;
GELINAS, RE ;
MILLER, AD .
JOURNAL OF VIROLOGY, 1987, 61 (05) :1639-1646
[4]   THE CONTRACTILITY OF FIBROBLASTS IN A COLLAGEN LATTICE IS REDUCED BY CORTICOSTEROIDS [J].
COULOMB, B ;
DUBERTRET, L ;
BELL, E ;
TOURAINE, R .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1984, 82 (04) :341-344
[5]   ANALYSIS OF THE MOUSE DHFR PROMOTER REGION - EXISTENCE OF A DIVERGENTLY TRANSCRIBED GENE [J].
CROUSE, GF ;
LEYS, EJ ;
MCEWAN, RN ;
FRAYNE, EG ;
KELLEMS, RE .
MOLECULAR AND CELLULAR BIOLOGY, 1985, 5 (08) :1847-1858
[6]   SAFE AND EFFICIENT GENERATION OF RECOMBINANT RETROVIRUSES WITH AMPHOTROPIC AND ECOTROPIC HOST RANGES [J].
DANOS, O ;
MULLIGAN, RC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (17) :6460-6464
[7]   LINEAGE-SPECIFIC EXPRESSION OF A HUMAN BETA-GLOBIN GENE IN MURINE BONE-MARROW TRANSPLANT RECIPIENTS RECONSTITUTED WITH RETROVIRUS-TRANSDUCED STEM-CELLS [J].
DZIERZAK, EA ;
PAPAYANNOPOULOU, T ;
MULLIGAN, RC .
NATURE, 1988, 331 (6151) :35-41
[8]   EXPRESSION OF A FOREIGN GENE IN MYELOID AND LYMPHOID-CELLS DERIVED FROM MULTIPOTENT HEMATOPOIETIC PRECURSORS [J].
KELLER, G ;
PAIGE, C ;
GILBOA, E ;
WAGNER, EF .
NATURE, 1985, 318 (6042) :149-154
[9]   EXPRESSION OF HUMAN ALPHA-GLOBIN AND MOUSE HUMAN HYBRID BETA-GLOBIN GENES IN MURINE HEMATOPOIETIC STEM-CELLS TRANSDUCED BY RECOMBINANT RETROVIRUSES [J].
LI, CL ;
DWARKI, VJ ;
VERMA, IM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1990, 87 (11) :4349-4353
[10]  
LI X, 1989, VIROLOGY, V171, P331