The therapeutic potential of RNA interference in controlling HIV-1 replication

Human immunodeficiency virus type 1 (HIV-1) has long been a major problem to handle. Its existence is incurable (yet) and has reached pandemic proportions despite strictly-controlled epidemiological surveillance. The current treatment regimen involves the use of multiple antiretroviral agents (known as HAART) is very complex and may harm patients through its serious risk of toxicities. Moreover, the continuing emergence of drug resistance further threaten the future therapy, thereby necessitates another treatment strategy i.e. specific and efficient with low or minimal toxicity. RNAi is a potent candidate for the future treatment of HIV-1. It involves an immune-based silencing mechanism (post transcriptional gene silencing/PTGS) that uses small sequence of RNA (21-25 nucleotides in length) to inhibit almost every genes expression, including HIV-1 RNA and its mRNA byproducts. Since RNAi uses sequence of base pairs, it can be designed very specific and homologues to silence the genes in favor. RNAi works either through binding with HIV-1 to inhibit provirus integration into cellular genome or with mRNA products to inhibit certain genes expression (e.g. p24/Gag, Vif, Rev) that plays an important role in HIV-1 infectivity to knockdown its virulence capacity. Given the need for a treatment modality that are sequence-specific and able to overcome the highly mutation rate of virus like HIV-1, also by its enormous power to inhibit HIV-1 expression through various target sites, it is considered essential to discuss the molecular mechanism of RNAi, progresses that have been achieved, and future directions for its use in clinical settings.