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Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

RNA Interference-Based Gene Expression Strategies Aimed at Sustained Therapeutic Inhibition of HIV

Author(s): Samantha Barichievy, Sheena Saayman, Patrick Arbuthnot and Marc S. Weinberg

Volume 9, Issue 12, 2009

Page: [1065 - 1078] Pages: 14

DOI: 10.2174/156802609789630901

Price: $65

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


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