Self-deleting suicide vectors (SDSV): selective killing of p53-deficient cancer cells.
A self-deleting retrovirus vector carrying a herpes simplex virus (HSV)-thymidine kinase suicide gene has been developed to selectively kill cancer cells expressing a dysfunctional p53 tumor suppressor protein. When cells containing functional p53 are infected with the virus, the integrated provirus and the HSV-thymidine kinase gene are deleted from the genome by site-specific recombination (Cre/loxP). In contrast, cells without p53 or cells expressing a DNA-binding mutant of p53 retain the provirus and become susceptible to killing by ganciclovir. This strategy provides a new concept for the selective killing of cancer cells that can be adapted to any other dysfunctional transcription factor expressed by different tumors.
Andreú
T
T
Laboratory for Molecular Hematology, Department of Hematology, University of Frankfurt Medical School, 60596 Frankfurt, Germany.
Ebensperger
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C
Westphal
E M
EM
Klenner
T
T
Stewart
A F
AF
Westhof
A
A
Müller
P
P
Knaus
R
R
von Melchner
H
H
D000818:Animals; D005260:Female; D015774:Ganciclovir / Q000493:pharmacokinetics / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011533:Proviruses / Q000235:genetics; D012190:Retroviridae / Q000235:genetics*; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D016662:Virus Integration / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D016159:Tumor Suppressor Protein p53; D013937:Thymidine Kinase; D015774:Ganciclovir