Elsevier

Neoplasia

Volume 1, Issue 4, October 1999, Pages 315-320
Neoplasia

A General Approach to the Non-Invasive Imaging of Transgenes Using Cis-Linked Herpes Simplex Virus Thymidine Kinase1

https://doi.org/10.1038/sj.neo.7900053Get rights and content
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Abstract

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.

Keywords

gene therapy
gene imaging
tumor
HSV1-tk
IRES

Abbreviations

EMCV
encephalomyocarditis virus
FCS
fetal calf serum
HSV1-tk
herpes simplex virus type one thymidine kinase
IRES
internal ribosomal entry site
PET
positron emission tomography
s.c.
subcutaneous

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1

This work was supported by NIH RO1 CA59350, NIH RO1 CA60706, NIH RO1 CA69769, NIH RO1 CA76117, DOE 86ER60407, the James McDonnell Foundation Scholars Award, the Gershel Foundation.