ABSTRACT
The discovery of RNAi (Fire et al., 1998) over the past few years has taken the biological and medical sciences by surprise (for reviews and guidance, see Couzin, 2002; Hammond et al., 2000; Hannon, 2002; Nykaneri et al., 2001; Sharp, 2001; Tuschl, 2002; Zamore, 2001; Zamore et al., 2000). The recent awarding of the 2006 Nobel Prize to the RNAi field is an early indication of its promise. After a short infancy as a post-transcriptional modification in C. elegans (Fire et al., 1998), as well as a quelling technique in plants (Jorgensen, 1990; Romano and Macino, 1992), it emerged as a powerful ubiquitous knockdown method that has quickly moved to vertebrates including human studies (Cullen, 2006). Ever since Tuschl and colleagues, in their milestone discovery in 2001 using chemically synthesized RNA duplexes (Caplen et al., 2001; Elbashir et al., 2001a, 2001b), uncovered the size exclusion secret that has precluded RNAi use in humans, the technique has shown a great deal of promise in gene validation, as a therapeutic (Behlke, 2006; Sachse and Echeverri, 2004; Sandy et al., 2005; Smith, 2006) and especially as an anti-infective agent (Novina et al., 2002; Qin et al., 2003; Wilson et al., 2003; Zamore and Aronin, 2003). Indeed, 21-27-long RNA duplexes with two-nucleotide overhang (Elbashir et al., 2001c) could bypass the immunological guards at more than 30 nucleotides to undergo RISC processing and antisense-strand-guided damage of the respective complementary mRNA (Martinez et al., 2002; Schwarz et al., 2002). Furthermore, the combination of RNAi discovery with the recent sequencing of several genomes, including human, has made the global study of gene function within a given genome in a living cell suddenly an attainable goal.
