RNA interference seemed poised to transform functional genomics and therapeutics with the 2001 publication of a paper by Tom Tuschl and colleagues showing that 21-base-pair (bp) RNA duplexes silence mammalian genes in a sequence-dependent manner.1 Though prior research demonstrated the effectiveness of double-stranded (ds)RNA as a posttranscriptional gene-silencing tool in plants and nematodes, its use in mammals was limited by the fact that dsRNAs larger than 30 bp can activate the interferon response through a PKR kinase-mediated pathway. After Tuschl's research was published, RNAi scientists were optimistic that so-called short interfering (si)RNAs were the answer to this problem.
Data derived from the Science Watch/Hot Papers database and the Web of Science (Thomson Scientific, Philadelphia) show that Hot Papers are cited 50 to 100 times more often than the average paper of the same type and age.
This optimism was squelched by a number of papers published in 2003 suggesting that ...
