The Race of 10 Synthetic RNAi-Based Drugs to the Pharmaceutical Market

Pharm Res. 2017 Jul;34(7):1339-1363. doi: 10.1007/s11095-017-2134-2. Epub 2017 Apr 7.


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.

Keywords: RNA interference; RNAi; miRNA; pharmaceutical market; siRNA.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Humans
  • MicroRNAs / antagonists & inhibitors*
  • Molecular Mimicry
  • Oligodeoxyribonucleotides, Antisense / therapeutic use
  • RNA Interference*
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / therapeutic use*


  • MicroRNAs
  • Oligodeoxyribonucleotides, Antisense
  • RNA, Small Interfering