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Exploiting the RNA interference pathway to counter hepatitis B virus replication

Authors

  • Patrick Arbuthnot,

    1. Hepatitis B Virus Research Programme, Department of Molecular Medicine and Haematology, University of the Witwatersrand, Private Bag 3, Wits 2050, South Africa
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  • Sergio Carmona,

    1. Hepatitis B Virus Research Programme, Department of Molecular Medicine and Haematology, University of the Witwatersrand, Private Bag 3, Wits 2050, South Africa
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  • Abdullah Ely

    1. Hepatitis B Virus Research Programme, Department of Molecular Medicine and Haematology, University of the Witwatersrand, Private Bag 3, Wits 2050, South Africa
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Patrick Arbuthnot, Hepatitis B Virus Research Programme, Department of Molecular Medicine and Haematology, University of the Witwatersrand, Private Bag 3, Wits 2050, South Africa.
Tel.: + 27-11-717-2365
Fax: + 27-11-717-2395
e-mail: arbuthnotpb@pathology.wits.ac.za

Abstract

Abstract: Chronic infection with hepatitis B virus (HBV) is endemic to sub-Saharan Africa and parts of Asia where persistence of the virus is commonly associated with complicating cirrhosis and hepatocellular carcinoma (HCC). Licensed therapies for HBV are partially effective in selected patients and development of novel treatments remains an important global medical objective. HBV has an unusually compact genome that restricts the ability of the virus to evade potentially therapeutic nucleic acid hybridization. Thus, exploiting the RNA interference (RNAi) pathway, which enables sequence-specific target RNA degradation using small interfering RNA (siRNA), is well suited to developing novel treatment for HBV infection. Several studies, both in vitro and in vivo, have demonstrated that HBV replication can be inhibited in transfected cells by synthetic siRNA duplexes and also Pol III-derived short hairpin RNA (shRNA) sequences. The effectiveness of anti-HBV sequences varies considerably, and is likely to result from differences in activation of the RNAi pathway by individual siRNA species. Exclusion of potentially toxic off-target effects and also development of efficient methods of hepatotropic nucleic acid delivery are important prerequisites before RNAi can be used successfully for anti-HBV treatment.

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