Transcriptional Targeted Gene Therapy for Hepatocellular Carcinoma by Adenovirus Vector
- 1 January 2001
- journal article
- review article
- Published by Springer Nature in Molecular Biotechnology
- Vol. 18 (3) , 243-250
- https://doi.org/10.1385/mb:18:3:243
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies with poor prognosis and is highly amenable to the development of novel therapeutic strategy. The human alpha-fetoprotein (AFP) gene is normally expressed in fetal liver and is transcriptionally silent in adult liver but overexpressed in HCC. In order to destroy AFP-producing HCC specifically, replication defective adenoviral vectors containing the transcriptional control elements of the AFP gene were designed. Expression of suicide genes by the AFP promoter/enhancer induced prodrug sensitivity in AFP (+) cells but not AFP (-) cells. The expression of suicide genes by ubiquitous promoter, however, showed no selectivity after prodrug treatment. Adenoviral vector transduced genes efficiently not only in vitro but also in vivo, and AFP-producing HCC xenografts regressed by transduction with transcriptionally targeted vectors and subsequent systemic administration of prodrug in animal model. Utilization of the transcriptional regulatory element to drive drug sensitive genes can be a promising strategy for cancer specific therapy.Keywords
This publication has 11 references indexed in Scilit:
- In vivo selective gene expression and therapy mediated by adenoviral vectors for human carcinoembryonic antigen-producing gastric carcinoma.1997
- Progress in Transcriptionally Targeted and Regulatable Vectors for Genetic TherapyHuman Gene Therapy, 1997
- In vivo gene therapy for alpha-fetoprotein-producing hepatocellular carcinoma by adenovirus-mediated transfer of cytosine deaminase gene.1997
- Gene Therapy for Cancer: What Have We Done and Where Are We Going?JNCI Journal of the National Cancer Institute, 1997
- Gene Therapy for α–Fetoprotein–Producing Human Hepatoma Cells by Adenovirus–Mediated Transfer of the Herpes Simplex Virus Thymidine Kinase GeneHepatology, 1996
- Efficient generation of recombinant adenoviruses using adenovirus DNA-terminal protein complex and a cosmid bearing the full-length virus genome.Proceedings of the National Academy of Sciences, 1996
- Adenovirus-mediated gene therapy of hepatocellular carcinoma using cancer-specific gene expression.1995
- Efficient gene activation in mammalian cells by using recombinant adenovirus expressing site-specific Cre recombinaseNucleic Acids Research, 1995
- Drug sensitivity ("suicide") genes for selective cancer chemotherapy.1994
- Efficient selection for high-expression transfectants with a novel eukaryotic vectorGene, 1991