Abstract
The naturally-occurring RNA interference (RNAi) pathway represents a powerful tool for the sequence-specific post-transcriptional silencing of gene expression. By exploiting the endogenous mammalian RNAi pathway, several expression-based strategies have been developed to inhibit human immunodeficiency virus (HIV) gene expression and replication. This approach potentially has utility as a protective ‘therapeutic vaccine’ of virus-susceptible lymphocytes. In this review we discuss new developments aimed at improving efficacy and delivery of novel RNAi-based gene expression antiviral strategies. Particular attention is given to advances in combinatorial gene expression systems that prevent the emergence of RNAi-resistant virus by simultaneously targeting multiple HIV targets. Potential usefulness of silencing host factors that are required for viral replication is also discussed. These approaches form the basis for a number of promising ongoing and future clinical trials aimed at providing an effective, safe and prolonged single-intervention therapy for HIV/AIDS.
Keywords: HIV, RNAi, shRNA, Gene therapy
Current Topics in Medicinal Chemistry
Title: RNA Interference-Based Gene Expression Strategies Aimed at Sustained Therapeutic Inhibition of HIV
Volume: 9 Issue: 12
Author(s): Samantha Barichievy, Sheena Saayman, Patrick Arbuthnot and Marc S. Weinberg
Affiliation:
Keywords: HIV, RNAi, shRNA, Gene therapy
Abstract: The naturally-occurring RNA interference (RNAi) pathway represents a powerful tool for the sequence-specific post-transcriptional silencing of gene expression. By exploiting the endogenous mammalian RNAi pathway, several expression-based strategies have been developed to inhibit human immunodeficiency virus (HIV) gene expression and replication. This approach potentially has utility as a protective ‘therapeutic vaccine’ of virus-susceptible lymphocytes. In this review we discuss new developments aimed at improving efficacy and delivery of novel RNAi-based gene expression antiviral strategies. Particular attention is given to advances in combinatorial gene expression systems that prevent the emergence of RNAi-resistant virus by simultaneously targeting multiple HIV targets. Potential usefulness of silencing host factors that are required for viral replication is also discussed. These approaches form the basis for a number of promising ongoing and future clinical trials aimed at providing an effective, safe and prolonged single-intervention therapy for HIV/AIDS.
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Cite this article as:
Barichievy Samantha, Saayman Sheena, Arbuthnot Patrick and Weinberg S. Marc, RNA Interference-Based Gene Expression Strategies Aimed at Sustained Therapeutic Inhibition of HIV, Current Topics in Medicinal Chemistry 2009; 9 (12) . https://dx.doi.org/10.2174/156802609789630901
DOI https://dx.doi.org/10.2174/156802609789630901 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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