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Retroviral transfer of HSV1-TK gene into human lung cancer cell line

✍ Scribed by Y. Hasegawa; N. Emi; K. Shimokata


Publisher
Springer
Year
1995
Tongue
English
Weight
603 KB
Volume
73
Category
Article
ISSN
0946-2716

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✦ Synopsis


We used a recombinant retrovirus as one of the potential vectors for human gene therapy to transfer a drug sensitivity gene into human lung cancer cells. The gene encoding the thymidine kinase (TK) of herpes simplex virus type 1 (HSVI) was used as the drug sensitivity gene. The antiherpes drugs acyclovir (ACV) and ganciclovir (GCV) were chosen to test the HSV 1-TK activity transferred into the human lung cancer cell lines. The rationale for this approach was that ACV and GCV are nucleoside analogs specifically converted by HSVI-TK to a toxic form capable of inhibiting DNA synthesis or disrupting cellular DNA replication. The results obtained from our experiments demonstrate that the retroviral vector-mediated HSV 1-TK gene transfer leads to ACV-and GCV-dependent cytotoxicity in human lung cancer cell lines, including both small-cell carcinoma and nonsmall-cell carcinoma. Although the gene transfer of HSV1-TK gene into tumor cells would be one model for gene therapy to control lung cancer, further investigations are necessary for the proper choice of the therapeutic gene and vector targeting such as tumor cell specific delivery of the gene or tumor cell specific expression of the transduced gene.


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