Progress in the use of RNA interference as a therapy for chronic hepatitis B virus infection 英文参考文献.docVIP

Weinberg and Arbuthnot Genome Medicine 2010,2:28 /content/2/4/28 REVIEW Progress in the use of RNA interference as a therapy for chronic hepatitis B virus infection Marc S Weinberg* and Patrick Arbuthnot viral replication. Although nucleoside and nucleotide Abstract analogs are well tolerated, the emergence of viral resis- tance remains a problem [3]. Currently, the nucleoside/ nucleotide analogs lamivudine (3TC), adefovir, entecovir and telbivudine are approved for use against HBV, with lamivudine being the most widely used. However, prolonged lamivudine monotherapy is often associated with the emergence of viral resistance to the drug [4]. Although cross-resistance to other nucleoside/nucleotide analogs, such as entecavir, has been demonstrated, the preferred ?rst line of therapy includes a combination of nucleoside/nucleotide analogs to limit the emergence of resistance (reviewed in [5]). IFN-α functions to augment the anti-HBV immune response and has been in wide- spread use for many years [6,7]. Currently, unmodi?ed and polyethylene glycol (PEG)-conjugated IFNs are licensed for therapy of HBV [8]. However, some patients are poorly responsive to IFN-α therapy, and it can induce adverse side e?ects, such as hepatic injury [9]. Moreover, IFN-α is often expensive and unavailable in resource- poor settings. Chronic infection with hepatitis B virus (HBV) occurs in approximately 6% of the world’s population and carriers of the virus are at risk for hepatocellular carcinoma and cirrhosis. Current treatment regimens, which include interferon-α and nucleoside/nucleotide analogs, are only partially eective and new treatment methods remain an important objective. Harnessing the RNA interference (RNAi) pathway to achieve post-transcriptional silencing of rogue genetic elements is an exciting avenue for development of novel therapeutic strategies. The specic and potent suppr