Inhibition of hepatitis C virus by nucleic acid-based antiviral approaches

Michael Frese, Ralf Bartenschlager

Research output: A Conference proceeding or a Chapter in BookChapter

1 Citation (Scopus)

Abstract

Persistent infection with the hepatitis C virus (HCV) is a major cause of acute and chronic liver disease and frequently leads to liver cirrhosis and hepatocellular carcinoma. Current treatment is based on a combination therapy with polyethylene glycol-conjugated interferon-alpha and ribavirin, but efficacy is limited and treatment is associated with severe side-effects. More efficient and selective drugs are therefore needed. Apart from small molecule inhibitors targeting the viral key enzymes, especially the NS3 proteinase and the NS5B RNA-dependent RNA polymerase, nucleic acid (NA)-based antiviral intervention is an attractive option. Originally, antisense oligo- nucleotides and ribozymes targeting highly conserved regions in the HCV genome have been developed. More recently, short interfering RNAs (siRNAs) were shown to potently block HCV RNA replication in cell culture. However, the high degree of sequence diversity between different HCV genotypes, the rapid evolution of quasispecies and the delivery of antivirally active NAs are challenging problems of NA-based therapies. Here, we will review the current state of NA-based approaches designed to interfere with HCV replication
Original languageEnglish
Title of host publicationNew Concepts of Antiviral Therapy
EditorsElke Bogner, Andreas Holzenburg
Place of PublicationThe Netherlands
PublisherSpringer
Chapter1.3
Pages47-86
Number of pages40
ISBN (Electronic)9780387310473
ISBN (Print)9780387310466
DOIs
Publication statusPublished - 2006
Externally publishedYes

Fingerprint

Hepacivirus
Nucleic Acids
Antiviral Agents
Virus Replication
RNA Replicase
Catalytic RNA
Ribavirin
Interferon-alpha
Liver Cirrhosis
Small Interfering RNA
Liver Diseases
Hepatocellular Carcinoma
Peptide Hydrolases
Chronic Disease
Nucleotides
Cell Culture Techniques
Genotype
Genome
RNA
Enzymes

Cite this

Frese, M., & Bartenschlager, R. (2006). Inhibition of hepatitis C virus by nucleic acid-based antiviral approaches. In E. Bogner, & A. Holzenburg (Eds.), New Concepts of Antiviral Therapy (pp. 47-86). The Netherlands: Springer. https://doi.org/10.1007/978-0-387-31047-3_3
Frese, Michael ; Bartenschlager, Ralf. / Inhibition of hepatitis C virus by nucleic acid-based antiviral approaches. New Concepts of Antiviral Therapy. editor / Elke Bogner ; Andreas Holzenburg. The Netherlands : Springer, 2006. pp. 47-86
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Frese, M & Bartenschlager, R 2006, Inhibition of hepatitis C virus by nucleic acid-based antiviral approaches. in E Bogner & A Holzenburg (eds), New Concepts of Antiviral Therapy. Springer, The Netherlands, pp. 47-86. https://doi.org/10.1007/978-0-387-31047-3_3

Inhibition of hepatitis C virus by nucleic acid-based antiviral approaches. / Frese, Michael; Bartenschlager, Ralf.

New Concepts of Antiviral Therapy. ed. / Elke Bogner; Andreas Holzenburg. The Netherlands : Springer, 2006. p. 47-86.

Research output: A Conference proceeding or a Chapter in BookChapter

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AB - Persistent infection with the hepatitis C virus (HCV) is a major cause of acute and chronic liver disease and frequently leads to liver cirrhosis and hepatocellular carcinoma. Current treatment is based on a combination therapy with polyethylene glycol-conjugated interferon-alpha and ribavirin, but efficacy is limited and treatment is associated with severe side-effects. More efficient and selective drugs are therefore needed. Apart from small molecule inhibitors targeting the viral key enzymes, especially the NS3 proteinase and the NS5B RNA-dependent RNA polymerase, nucleic acid (NA)-based antiviral intervention is an attractive option. Originally, antisense oligo- nucleotides and ribozymes targeting highly conserved regions in the HCV genome have been developed. More recently, short interfering RNAs (siRNAs) were shown to potently block HCV RNA replication in cell culture. However, the high degree of sequence diversity between different HCV genotypes, the rapid evolution of quasispecies and the delivery of antivirally active NAs are challenging problems of NA-based therapies. Here, we will review the current state of NA-based approaches designed to interfere with HCV replication

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Frese M, Bartenschlager R. Inhibition of hepatitis C virus by nucleic acid-based antiviral approaches. In Bogner E, Holzenburg A, editors, New Concepts of Antiviral Therapy. The Netherlands: Springer. 2006. p. 47-86 https://doi.org/10.1007/978-0-387-31047-3_3