Ten years after Fire and Melo's Nobel Prize for discovery of gene silencing by 
double-stranded RNA, a remarkable progress was achieved in RNA interference 
(RNAi). Changes in the chemical structure of synthetic oligonucleotides make 
them more stable and specific, and new delivery strategies became progressively 
available. The attention of pharmaceutical industry rapidly turned to RNAi, as 
an opportunity to explore new drug targets. This review addresses nine 
small-interfering RNAs (siRNAs) and one unique microRNA (miRNA) inhibitor, which 
entered the phase 2-3 clinical trials. The siRNAs in focus are PF-04523655, 
TKM-080301, Atu027, SYL040012, SYL1001, siG12D-LODER (phase 2), QPI-1002, 
QPI-1007, and patisiran (phase 3). Regarding miRNAs, their content can be down- 
or up-regulated, by using miRNA inhibitors (AntimiRs) or miRNA mimics. 
Miravirsen is an AntimiR-122 for hepatitis C virus infection. The flexibility of 
RNAi technology is easily understood taking into account: (i) the different drug 
targets (i.e. p53, caspase 2, PKN3, β2-adrenergic receptor, mutated KRAS, 
microRNAs); (ii) therapeutic conditions, including ophthalmic diseases, kidney 
injury, amyloidosis, pancreatic cancer, viral hepatitis; and (iii) routes of 
administration (ocular, intravenous, subcutaneous, intratumoral). Although some 
issues are still matters of concern (delivery, toxicity, cost, and biological 
barriers), RNAi definitively opens a wide avenue for drug development.