An Adenovirus Vector Containing the Suicide Gene Thymidine Kinase for a Broad Application in Cancer Gene Therapy

Memórias do Instituto Oswaldo Cruz

Gs Magalhães¹  Ar Muotri¹  Mcn Marchetto¹  Cfm Menck¹  Am Ventura¹ 

[1] ,Universidade de São Paulo Instituto de Ciências Biomédicas Departamento de MicrobiologiaSão Paulo SP ,Brasil

关键词: ganciclovir;    adenovirus;    thymidine kinase;    cancer;    gene therapy;   

DOI  :  10.1590/S0074-02762002000400018

来源: SciELO

【 摘 要 】

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.

【 授权许可】

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