Oligonucleotide therapies for nonalcoholic steatohepatitis

Sixu Li; Feng Xiong; Songbo Zhang; Jinghua Liu; Guangping Gao; Jun Xie; Yi Wang

doi:10.1016/j.omtn.2024.102184

Oligonucleotide therapies for nonalcoholic steatohepatitis

Mol Ther Nucleic Acids. 2024 Mar 30;35(2):102184. doi: 10.1016/j.omtn.2024.102184. eCollection 2024 Jun 11.

Authors

Sixu Li¹, Feng Xiong², Songbo Zhang³, Jinghua Liu^{4

5}, Guangping Gao^{4

5

6

7}, Jun Xie^{4

5

7}, Yi Wang¹

Affiliations

¹ Department of Pathophysiology, West China College of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610066, China.
² Department of Cardiology, The Third People's Hospital of Chengdu, Chengdu 610031, China.
³ Department of Breast Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China.
⁴ Horae Gene Therapy Center, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
⁵ Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
⁶ Li Weibo Institute for Rare Diseases Research, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
⁷ Viral Vector Core, University of Massachusetts Chan Medical, School, Worcester, MA 01605, USA.

Abstract

Nonalcoholic steatohepatitis (NASH) represents a severe disease subtype of nonalcoholic fatty liver disease (NAFLD) that is thought to be highly associated with systemic metabolic abnormalities. It is characterized by a series of substantial liver damage, including hepatocellular steatosis, inflammation, and fibrosis. The end stage of NASH, in some cases, may result in cirrhosis and hepatocellular carcinoma (HCC). Nowadays a large number of investigations are actively under way to test various therapeutic strategies, including emerging oligonucleotide drugs (e.g., antisense oligonucleotide, small interfering RNA, microRNA, mimic/inhibitor RNA, and small activating RNA) that have shown high potential in treating this fatal liver disease. This article systematically reviews the pathogenesis of NASH/NAFLD, the promising druggable targets proven by current studies in chemical compounds or biological drug development, and the feasibility and limitations of oligonucleotide-based therapeutic approaches under clinical or pre-clinical studies.

Keywords: ASO; MT: Oligonucleotides: Therapies and Applications; NAFLD; NASH; RNAi; miRNA; oligonucleotide drug; siRNA.

Publication types

Review