Antisense oligonucleotide is a promising intervention for liver diseases

Abstract

As the body’s critical metabolic organ, the liver plays an essential role in maintaining proper body homeostasis. However, as people’s living standards have improved and the number of unhealthy lifestyles has increased, the liver has become overburdened. These have made liver disease one of the leading causes of death worldwide. Under the influence of adverse factors, liver disease progresses from simple steatosis to hepatitis, to liver fibrosis, and finally to cirrhosis and cancer, followed by increased mortality. Until now, there has been a lack of accepted effective treatments for liver disease. Based on current research, antisense oligonucleotide (ASO), as an alternative intervention for liver diseases, is expected to be an effective treatment due to its high efficiency, low toxicity, low dosage, strong specificity, and additional positive characteristics. In this review, we will first introduce the design, modification, delivery, and the mechanisms of ASO, and then summarize the application of ASO in liver disease treatment, including in non-alcoholic fatty liver disease (NAFLD), hepatitis, liver fibrosis, and liver cancer. Finally, we discuss challenges and perspectives on the transfer of ASO drugs into clinical use. This review provides a current and comprehensive understanding of the integrative and systematic functions of ASO for its use in liver disease.

The Coming Age of Antisense Oligos for the Treatment of Hepatic Ischemia/Reperfusion (IRI) and Other Liver Disorders: Role of Oxidative Stress and Potential Antioxidant Effect

“…Alternatively, delivering ASOs to specific cell types via targeted endocytosis remains a challenge that needs more attention. In the liver, the use of Gal-Nac-coupled ASO represents a significant advance, but for other organ systems, the future challenge will be to identify cell surface target receptors that allow ASO vacuolization, especially considering the inefficiencies of the endosomal pathway [133]. Studies have shown that conjugating ASOs to glucagon-like peptide 1 (GLP1) enhances targeted knockdown in pancreatic β-cells [134] and that targeting coat protein complex II (COPII) vesicles, typically involved in ER-Golgi transport, can re-locate ASOs to late endosomes (LEs) vesicles upon incubation [135].…”