An update on the therapeutic role of RNAi in NAFLD/NASH

Prog Mol Biol Transl Sci. 2024:204:45-67. doi: 10.1016/bs.pmbts.2023.12.005. Epub 2023 Dec 29.

Abstract

Unhealthy lifestyles have given rise to a growing epidemic of metabolic liver diseases, including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). NAFLD often occurs as a consequence of obesity, and currently, there is no FDA-approved drug for its treatment. However, therapeutic oligonucleotides, such as RNA interference (RNAi), represent a promising class of pharmacotherapy that can target previously untreatable conditions. The potential significance of RNAi in maintaining physiological homeostasis, understanding pathogenesis, and improving metabolic liver diseases, including NAFLD, is discussed in this article. We explore why NAFLD/NASH is an ideal target for therapeutic oligonucleotides and provide insights into the delivery platforms of RNAi and its therapeutic role in addressing NAFLD/NASH.

Keywords: Antisense oligonucleotide; Fatty liver; RNA interference; SiRNA; Steatosis.

MeSH terms

  • Humans
  • Liver Cirrhosis
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Non-alcoholic Fatty Liver Disease* / therapy
  • Oligonucleotides / therapeutic use
  • RNA Interference

Substances

  • Oligonucleotides