RNA Interference for Viral Infections

School of Medical Science, Griffith University, Gold Coast Campus, QLD 4222, Qld, Australia. .
Current drug targets (Impact Factor: 3.02). 05/2012; 13(11):1411-20. DOI: 10.2174/138945012803530161
Source: PubMed


The treatment of viral infections has relied on pre-emptive vaccination or use of a limited range of anti-viral drugs. However, the majority of viruses have no available drugs and treatment is merely supportive. RNA interference (RNAi) offers the ability to directly and rapidly treat virus infections via the targeting of viral genes. Indeed, clinical trials have already been undertaken with promising results. Here we review the current state of the RNAi field for the treatment of viral infections such as HIV, human papillomavirus and HCV. We also review novel strategies including the concept of targeting self-genes to limit viral infection and activating the immune system for improved outcomes. Finally we examine innovative approaches being pursued at the Australian Infectious Diseases Research Centre including the use of highthroughput siRNA screens to identify new antiviral targets.

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Available from: Fawzi Bokhari, Oct 09, 2015
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    • "The exhaustive work undertaken in preclinical studies (both in vitro in culture cells and in vivo in animals) has shown that RNAi therapeutic against viral infections is highly effective at reducing virus replication and also useful as a tool to rapidly identify novel antiviral drug targets via large-scale screens for a number of viral infections [175]. Several novel viral targets have been identified and are the subject of intense research and development, but definitive evidence is lacking from well-controlled studies that demonstrate the effectiveness in these infection diseases [176]. "
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    ABSTRACT: The efforts made to develop RNAi-based therapies have led to productive research in the field of infections in humans, such as hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), human cytomegalovirus (HCMV), herpetic keratitis, human papillomavirus, or influenza virus. Naked RNAi molecules are rapidly digested by nucleases in the serum, and due to their negative surface charge, entry into the cell cytoplasm is also hampered, which makes necessary the use of delivery systems to exploit the full potential of RNAi therapeutics. Lipid nanoparticles (LNP) represent one of the most widely used delivery systems for in vivo application of RNAi due to their relative safety and simplicity of production, joint with the enhanced payload and protection of encapsulated RNAs. Moreover, LNP may be functionalized to reach target cells, and they may be used to combine RNAi molecules with conventional drug substances to reduce resistance or improve efficiency. This review features the current application of LNP in RNAi mediated therapy against viral infections and aims to explore possible future lines of action in this field.
    BioMed Research International 08/2014; 2014:161794. DOI:10.1155/2014/161794 · 3.17 Impact Factor
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    • "RNAi screens have been used for a number of viral infections such as HIV, Influenza virus, HCV, Dengue virus, and West Nile virus (reviewed in [131]). From these a number of novel targets have been identified and are the subject of intense research and development. "
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    ABSTRACT: Human Papillomavirus (HPV)-induced diseases are a significant burden on our healthcare system and current therapies are not curative. Vaccination provides significant prophylactic protection but effective therapeutic treatments will still be required. RNA interference (RNAi) has great promise in providing highly specific therapies for all HPV diseases yet this promise has not been realised. Here we review the research into RNAi therapy for HPV in vitro and in vivo and examine the various targets and outcomes. We discuss the idea of using RNAi with current treatments and address delivery of RNAi, the major issue holding back clinical adoption. Finally, we present our view of a potential path to the clinic.
    The Open Virology Journal 12/2012; 6:204-15. DOI:10.2174/1874357901206010204
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    ABSTRACT: RNA viruses show enormous capacity to evolve and adapt to new cellular and molecular contexts, a consequence of mutations arising from errors made by viral RNA-dependent RNA polymerase during replication. Sequence variation must occur, however, without compromising functions essential for the completion of the viral cycle. RNA viruses are safeguarded in this respect by their genome carrying conserved information that does not code only for proteins but also for the formation of structurally conserved RNA domains that directly perform these critical functions. Functional RNA domains can interact with other regions of the viral genome and/or proteins to direct viral translation, replication and encapsidation. They are therefore potential targets for novel therapeutic strategies. This review summarises our knowledge of the functional RNA domains of human RNA viruses and examines the achievements made in the design of antiviral compounds that interfere with their folding and therefore their function. Copyright © 2013 John Wiley & Sons, Ltd.
    Reviews in Medical Virology 11/2013; 23(6). DOI:10.1002/rmv.1756 · 5.57 Impact Factor
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