Development of siRNA Therapeutics for the Treatment of Liver Diseases

Methods Mol Biol. 2021;2282:57-75. doi: 10.1007/978-1-0716-1298-9_5.


Small interfering RNA (siRNA)-based therapeutics holds the promise to treat a wide range of human diseases that are currently incurable using conventional therapies. Most siRNA therapeutic efforts to date have focused on the treatment of liver diseases due to major breakthroughs in the development of efficient strategies for delivering siRNA drugs to the liver. Indeed, the development of lipid nanoparticle-formulated and GalNAc-conjugated siRNA therapeutics has resulted in recent FDA approvals of the first siRNA-based drugs, patisiran for the treatment of hereditary transthyretin amyloidosis and givosiran for the treatment of acute hepatic porphyria, respectively. Here, we describe the current strategies for delivering siRNA drugs to the liver and summarize recent advances in clinical development of siRNA therapeutics for the treatment of liver diseases.

Keywords: ASGPR; Gene silencing; Lipid nanoparticle; Liver; N-Acetylgalactosamine; RNAi; siRNA.

Publication types

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

MeSH terms

  • Acetylgalactosamine / analogs & derivatives
  • Acetylgalactosamine / therapeutic use
  • Amyloid Neuropathies, Familial / genetics
  • Amyloid Neuropathies, Familial / metabolism
  • Amyloid Neuropathies, Familial / therapy
  • Animals
  • Gene Transfer Techniques
  • Humans
  • Liver Diseases / genetics
  • Liver Diseases / metabolism
  • Liver Diseases / therapy*
  • Porphyrias, Hepatic / diagnosis
  • Porphyrias, Hepatic / metabolism
  • Porphyrias, Hepatic / therapy
  • Pyrrolidines / therapeutic use
  • RNA Interference*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA, Small Interfering / therapeutic use*
  • RNAi Therapeutics*


  • Pyrrolidines
  • RNA, Small Interfering
  • patisiran
  • Acetylgalactosamine
  • givosiran

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related