Gene therapy for chronic viral hepatitis: Ribozymes, antisense oligonucleotides, and dominant negative mutants
✍ Scribed by F von Weizsäcker; S Wieland; J Köck; W Offensperger; S Offensperger; D Moradpour; H E Blum
- Publisher
- John Wiley and Sons
- Year
- 1997
- Tongue
- English
- Weight
- 411 KB
- Volume
- 26
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
HEPATOLOGY Concise Review
and safety, need to be solved before gene therapy of viral Gene Therapy for Chronic Viral hepatitis B or C will complement existing therapeutic and preventive strategies. Hepatitis: Ribozymes, Antisense Molecular biology and recombinant DNA technology increasingly contribute to the diagnosis, therapy, and preven-Oligonucleotides, and Dominant tion of human diseases. Molecular methods allow the specific detection and molecular characterization of hepatitis B virus Negative Mutants (HBV) DNA or hepatitis C virus (HCV) RNA from serum, cells or tissues. In addition, such analyses have led to a better understanding of the pathogenesis of chronic hepatitis B and FRITZ VON WEIZSA ¨CKER, STEFAN WIELAND, C and their associated diseases, including liver cirrhosis and JOSEF KO ¨CK, WOLF-BERNHARD OFFENSPERGER, hepatocellular carcinoma. 1 SILKE OFFENSPERGER, DARIUS MORADPOUR, Antiviral strategies are aimed at one or several steps of the AND HUBERT E. BLUM viral life cycle: attachment of the virus to the cell membrane, internalization and uncoating, viral replication and gene expression, virus assembly, and finally virion export.
In view of Viral infections can be viewed as acquired genetic diseases the limited efficacy of currently available therapies of chronic and represent a major potential application of gene therapy. viral hepatitis B or C, 2 several genetic antiviral strategies are For the treatment of hepatitis B virus (HBV) or hepatitis C being explored. Apart from DNA vaccination, 3-8 which has virus (HCV) infection several antiviral strategies aimed at been experimentally explored already as an antiviral strategy blocking viral gene expression or function are being exin HBV infection 9-13 as well as HCV infection, [14][15][16] an attracplored. Ribozymes, antisense oligonucleotides, and dominant tive genetic antiviral concept is blocking viral gene expresnegative mutants strongly inhibit viral replication and gene sion or function at different levels of the viral life cycle (Fig. expression in experimental systems in vitro and in some mod-1). In the context of this review, gene therapy is defined as els in vivo. Despite exciting recent developments, a number the introduction of foreign nucleic acids into cells or tissues of issues, such as gene transfer, stability, toxicity, resistance, with a therapeutic benefit. 17 In the following, we will briefly FIG. 1. Strategies aimed at blocking gene expression or function: 1) decoy strategy; 2) triple helix formation (transcription), decoy or antisense strategy (reverse transcription); 3) ribozymes; 4) antisense strategy; and 5) interfering peptides or proteins.
Abbreviations: HBV, hepatitis B virus; HCV, hepatitis C virus; DN, dominant negative; DHBV, duck hepatitis B virus.