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Exploiting the RNA interference pathway to counter hepatitis B virus replication
Author(s) -
Arbuthnot Patrick,
Carmona Sergio,
Ely Abdullah
Publication year - 2005
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2004.0966.x
Subject(s) - rna interference , hepatitis b virus , small hairpin rna , small interfering rna , virology , rna , biology , hepatitis b virus pre beta , nucleic acid , virus , viral replication , hepatocellular carcinoma , hepatitis c virus , cancer research , gene , hepatitis b virus dna polymerase , genetics
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.