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von Laer, D.* ; Baum, C.* ; Protzer, U.

Antiviral gene therapy.

In: Antiviral Strategies.. Berlin ; Heidelberg: Springer, 2009. 265-297 (Handb. Exp. Pharmacol. ; 189)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
This chapter describes the major gene therapeutic approaches for viral infections. The vast majority of published approaches target severe chronic viral infections such as hepatitis B or C and HIV infection. Two basic gene therapy strategies are introduced here. The first involves the expression of a protein or an RNA that inhibits viral replication by targeting crucial steps of the viral life cycle or by interfering with a cellular factor required for virus replication. The major limitation of this approach is that primary levels of gene modification have generally not been sufficient to reduce the availability of target cells permissive for virus replication to a level that significantly decreases overall viral load. Thus, investigators have banked on the expectation that gene-protected cells have a sufficient selective advantage to accumulate and gain prevalence over time, a prediction that so far could not be confirmed in clinical trials. In vivo levels of gene modification can be improved, however, by introducing an additional selectable marker. In addition, a secreted antiviral gene product that exerts a bystander effect could significantly reduce overall virus replication despite relatively low levels of gene modification. In addition to these direct antiviral approaches, several strategies have been developed that employ or aim to enhance host immune responses. The innate immune response has been enhanced, for example, by the in vivo expression of interferons. Alternatively, T cells can be grafted with recombinant receptors to boost adaptive virus-specific immunity. These approaches are especially promising for chronic virus infection, where natural immune responses are evidently not sufficient to effectively control virus replication.
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Publication type Article: Edited volume or book chapter
Editors Kräusslich, H.G.* ; Bartenschlager, R.*
Corresponding Author
Keywords virostatic agent
ISSN (print) / ISBN 0171-2004
Book Volume Title Antiviral Strategies.
Journal Handbook of Experimental Pharmacology
Quellenangaben Volume: 189, Issue: , Pages: 265-297 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Berlin ; Heidelberg
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)