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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060 EISSN: 1678-8060
Vol. 97, No. 4, 2002, pp. 547-552
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Bioline Code: oc02104
Full paper language: English
Document type: Research Article
Document available free of charge
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Memórias do Instituto Oswaldo Cruz, Vol. 97, No. 4, 2002, pp. 547-552
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An Adenovirus Vector Containing the Suicide Gene Thymidine Kinase for a Broad Application in Cancer Gene Therapy
GS Magalhães; AR Muotri; MCN Marchetto; CFM Menck & AM Ventura
Abstract
Treatment of cancer using gene therapy is based on adding
a property to the cell leading to its elimination. One possibility is the
use of suicide genes that code for enzymes that transform a pro-drug into
a cytotoxic product. The most extensively used is the herpes simplex virus
thymidine kinase (TK) gene, followed by administration of the antiviral
drug ganciclovir (GCV). The choice of the promoter to drive the transcription
of a transgene is one of the determinants of a given transfer vector usefulness,
as different promoters show different efficiencies depending on the target
cell type. In the experiments presented here, we report the construction
of a recombinant adenovirus carrying TK gene (Ad-TK) driven by three strong
promoters (P
CMV IE
, SV40 and EN1) and its effectiveness in two cell types. Human HeLa and
mouse CCR2 tumor cells were transduced with Ad-TK and efficiently killed
after addition of GCV. We could detect two sizes of transcripts of TK gene,
one derived from the close together P
CMV IE
/SV40 promoters and the other from the 1.5 Kb downstream EN1 promoter. The
relative amounts of these transcripts were different in each cell type thus
indicating a higher flexibility of this system.
Keywords
ganciclovir - adenovirus - thymidine kinase - cancer - gene therapy
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