RNAi therapeutic and its innovative biotechnological evolution

Biotechnol Adv. 2019 Sep-Oct;37(5):801-825. doi: 10.1016/j.biotechadv.2019.04.012. Epub 2019 Apr 26.


Recently, United States Food and Drug Administration (FDA) and European Commission (EC) approved Alnylam Pharmaceuticals' RNA interference (RNAi) therapeutic, ONPATTRO™ (Patisiran), for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. This is the first RNAi therapeutic all over the world, as well as the first FDA-approved treatment for this indication. As a milestone event in RNAi pharmaceutical industry, it means, for the first time, people have broken through all development processes for RNAi drugs from research to clinic. With this achievement, RNAi approval may soar in the coming years. In this paper, we introduce the basic information of ONPATTRO and the properties of RNAi and nucleic acid therapeutics, update the clinical and preclinical development activities, review its complicated development history, summarize the key technologies of RNAi at early stage, and discuss the latest advances in delivery and modification technologies. It provides a comprehensive view and biotechnological insights of RNAi therapy for the broader audiences.

Keywords: Antisense oligonucleotide; Chemical modification; GalNAc; Liposome; Nucleic acid therapeutics; ONPATTRO; Patisiran; RNA interference; siRNA; siRNA delivery.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biotechnology / economics
  • Biotechnology / methods*
  • Clinical Trials as Topic
  • Drug Approval
  • Drug Delivery Systems / adverse effects
  • Drug Delivery Systems / methods*
  • Humans
  • Oligonucleotides / therapeutic use
  • RNA, Small Interfering / therapeutic use
  • RNAi Therapeutics*


  • Oligonucleotides
  • RNA, Small Interfering
  • Inotersen
  • patisiran
  • bevasiranib
  • revusiran