RNA interference-based gene expression strategies aimed at sustained therapeutic inhibition of HIV.
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.
Barichievy
Samantha
S
Antiviral Gene Therapy Research Unit, Department of Molecular Medicine and Haematology, University of Witwatersrand, Johannesburg, South Africa.
Saayman
Sheena
S
Arbuthnot
Patrick
P
Weinberg
Marc S
MS
D019380:Anti-HIV Agents / Q000627:therapeutic use; D015870:Gene Expression; D006678:HIV / Q000235:genetics*; D034622:RNA Interference; D012367:RNA, Viral / Q000235:genetics
D019380:Anti-HIV Agents; D012367:RNA, Viral