Gene transfer using a disabled herpes virus vector containing the EMCV IRES allows multiple gene expression in vitro and in vivo

被引:22
作者
Wagstaff, MJD [1 ]
Lilley, CE [1 ]
Smith, J [1 ]
Robinson, MJ [1 ]
Coffin, RS [1 ]
Latchman, DS [1 ]
机构
[1] UCL, Sch Med, Windeyer Inst Med Sci, Dept Mol Pathol, London W1P 6DB, England
基金
英国医学研究理事会;
关键词
IRES; HSV-1; gene delivery; bicistronic vectors;
D O I
10.1038/sj.gt.3300754
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The design of recombinant HSV-1 vectors for delivery of transgenes to the central nervous system is undergoing constant development. Problems associated with the construction and use of such vectors include the requirement for detection of recombinant versus nonrecombinant virus in vitro and also the identification of transduced cells in vivo. This could be overcome by the insertion of reporter genes such as lacZ or green fluorescent protein (GFP) under a separate promoter to the transgene to be expressed. In this case, however, reporter gene expression does not necessarily confirm transgene expression as a separate RNA must be produced. This study reports the use of an encephalomyocarditis virus internal ribosome entry site (IRES) to enable the translation of two reporter genes from a single mRNA transcript driven by the same promoter within a disabled HSV vector, and discusses the potential advantages of this approach.
引用
收藏
页码:1566 / 1570
页数:5
相关论文
共 12 条
[1]  
Coffin RS, 1996, GENE THER, V3, P560
[2]  
Coffin RS, 1996, GENE THER, V3, P886
[3]   THE ENCEPHALOMYOCARDITIS VIRUS INTERNAL RIBOSOME ENTRY SITE ALLOWS EFFICIENT COEXPRESSION OF 2 GENES FROM A RECOMBINANT PROVIRUS IN CULTURED-CELLS AND IN EMBRYOS [J].
GHATTAS, IR ;
SANES, JR ;
MAJORS, JE .
MOLECULAR AND CELLULAR BIOLOGY, 1991, 11 (12) :5848-5859
[4]   Construction of adenoviral and retroviral vectors coexpressing the genes encoding the hepatitis B surface antigen and B7-1 protein [J].
He, XS ;
Rivkina, M ;
Robinson, WS .
GENE, 1996, 175 (1-2) :121-125
[5]  
Ho Dora Y., 1995, P133, DOI 10.1016/B978-012397570-6/50011-3
[6]  
HO DY, 1995, J NEUROCHEM, V65, P842
[7]  
HOWARD MK, IN PRESS GENE THERAP
[8]   Utilization of the herpes simplex virus type 1 latency-associated regulatory region to drive stable reporter gene expression in the nervous system [J].
Lachmann, RH ;
Efstathiou, S .
JOURNAL OF VIROLOGY, 1997, 71 (04) :3197-3207
[9]   LONG-TERM PROMOTER ACTIVITY DURING HERPES-SIMPLEX VIRUS LATENCY [J].
LOKENSGARD, JR ;
BLOOM, DC ;
DOBSON, AT ;
FELDMAN, LT .
JOURNAL OF VIROLOGY, 1994, 68 (11) :7148-7158
[10]  
Okada H, 1996, GENE THER, V3, P957