RNA interference (RNAi) refers to the conserved sequence-specific degradation of message RNA mediated by small interfering (si)RNA duplexes 21–25 nucleotides in length. Given the ability to specifically silence any gene of interest, siRNAs offers several advantages over conventional drugs as potential therapeutic agents for the treatment of human maladies including cancers, genetic disorders, and infectious diseases. Antiviral RNAi strategies have received much attention and several compounds are currently being tested in clinical trials. In particular, the development of siRNA-based HIV (human immunodeficiency virus) therapeutics has progressed rapidly and many recent studies have shown that the use of RNAi could inhibit HIV-1 replication by targeting a number of viral or cellular genes. Therefore, the present chapter mainly focuses on the recent progress of RNAi-based anti-HIV gene therapeutics, with particular atten- tion to molecular targets and delivery strategies of the siRNAs.
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