Metabolic Dysfunction-Associated Steatotic Liver Disease and Emerging Oligonucleotide Therapies
Year: 2026
Type: article
Abstract: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is a prevalent chronic liver condition characterized by pathological fat accumulation in hepatocytes, with a global prevalence of approximately 30% that continues to rise. Current treatment options are limited, highlighting an urgent need for novel therapeutic strategies. This review systematically examines the emerging promise of oligonucleotide-based drugs for MASLD treatment, including antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA (miRNA) mimic or inhibitor, small activating RNA (saRNA) and splicing-switching oligonucleotide (SSO). We summarize the mechanisms of action of these therapeutics, which enable precise targeting of genes involved in MASLD pathogenesis. Furthermore, the review explores advanced delivery systems, particularly N-acetylgalactosamine (GalNAc) conjugation, which enhances hepatocyte-specific targeting. Finally, we discuss the current challenges facing oligonucleotide drug development and outline future directions for this rapidly advancing field, underscoring its potential to revolutionize MASLD management.
DOI: 10.7150/ijbs.127996
Institutions: Chinese Academy of Sciences, Shenzhen Institutes of Advanced Technology, Shenzhen Institute of Synthetic Biology, Fujian Agriculture and Forestry University, Shenzhen University of Advanced Technology, University of Hong Kong, Tianjin University of Science and Technology, State Key Laboratory of Food Nutrition and Safety, Guangzhou Women and Children Medical Center, State Key Laboratory of Pharmaceutical Biotechnology, Guangzhou Medical University
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,337
Award: G4617904542
OpenAlex ID: W7128910946