Jim Apostolopoulos Pages 587 - 598 ( 12 )
The ability to silence specific genes of choice consistently and efficiently has always been a major goal for scientists. The emerging field of RNA interference (RNAi), a process in which target mRNAs are degraded by small interfering RNA (siRNA), may indeed provide this long sought after tool. The importance of this technology has been highlighted recently by Science, which has voted the RNAi discoveries as the “ & ;Breakthrough of the Year” in 2002. Essentially, RNAi involves an initiation and an effector step whereby introduced dsRNA is digested into 19-21 duplex siRNA by cleavage with Dicer and siRNA binds to an RNA-induced silencing complex (RISC). Activation of RISC targets the homologous sequence (transcript) and results in the cleavage of mRNA. The models of this RNAi mechanism and its applications, derived from biochemical and genetic approaches, are described in this minireview. So far, RNAi has proven to be a useful technique for genomic studies in C.elegans, D.melanogaster and various plants, for example. The use of RNAi has also been invaluable in studies in which morphological and developmental variability between species was investigated. Targeted, sequence specific siRNAs that suppress or silence gene expression have the potential to be in great demand as tools for for the treatment of human disease. There have already been several studies that have utilized siRNA to inhibit HIV-1 infection and replication, for example. The expansion of RNAi for biomedical therapeutics seems inevitable. This minireview analytically summarizes the advantages and the current and future potential of RNAi technology whilst simultaneously investigating any shortfalls or difficulties. Importantly, in vitro and in vivo applications in the laboratory and in human disease models are also described.
sirna, rnai, co-suppression, ptgs
Centre for Inflammatory Diseases, Monash University Department of Medicine, Level 5 E Block,Monash Medical Centre, 246 Clayton Road Clayton, Victoria 3168, Australia.