A General Approach to the Non-Invasive Imaging of Transgenes Using Cis-Linked Herpes Simplex Virus Thymidine Kinase

A General Approach to the Non-Invasive Imaging of Transgenes Using Cis-Linked Herpes Simplex Virus Thymidine Kinase

Non-invasive imaging of gene expression opens new prospects for the study of transgenic animals and the implementation of genetically based therapies in patients. We have sought to establish a general paradigm to enable whole body non-invasive imaging of any transgene. We show that the expression an...

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Bibliographic Details
Published in:Neoplasia (New York, N.Y.) Vol. 1; no. 4; pp. 315 - 320
Main Authors: Tjuvajev, Juri G., Joshi, Arjun, Callegari, James, Lindsley, Laura, Joshi, Revathi, Balaton, Julius, Find, Ronald, Larso, Steven M., Sadelain, Michel, Blasberg, Ronald G.
Format: Journal Article
Language:English
Published: United States Elsevier Inc 01-10-1999
Elsevier
Subjects:
Animals
beta-Galactosidase - metabolism
Blotting, Southern
Diagnostic Imaging - methods
Escherichia coli - enzymology
Gamma Rays
gene imaging
gene therapy
Genetic Therapy - methods
Genetic Vectors
HSV1-tk
IRES
Lac Operon - genetics
Neoplasm Transplantation
Promoter Regions, Genetic
Rats
Rats, Sprague-Dawley
Retroviridae - genetics
Simplexvirus - enzymology
Thymidine Kinase - genetics
Transcription, Genetic
Transduction, Genetic
Transgenes
tumor
Tumor Cells, Cultured
gene imaging
IRES
tumor
FCS
gene therapy
s.c
HSV1-tk
EMCV
PET
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Summary:Non-invasive imaging of gene expression opens new prospects for the study of transgenic animals and the implementation of genetically based therapies in patients. We have sought to establish a general paradigm to enable whole body non-invasive imaging of any transgene. We show that the expression and imaging of HSV1-tk (a marker gene) can be used to monitor the expression of the LacZ gene (a second gene) under the transcriptional control of a single promoter within a bicistronic unit that includes a type II internal ribosomal entry site. In cells bearing a single copy of the vector, the expression of the two genes is proportional and constant, both in vitro and in vivo. We demonstrate that non-invasive imaging of HSV1-tk gene accurately reflects the topology and activity of the other cis-linked transgene.
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SourceType-Scholarly Journals-1
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content type line 23
ISSN:1476-5586
1522-8002
1476-5586
1522-8002
DOI:10.1038/sj.neo.7900053