Related Experiment Video
Updated: Oct 29, 2025
Author Spotlight: Innovative Cancer Therapies with Iron Oxide Nanoparticles for Glioblastoma Treatment
Published on: September 27, 2024
Liver-Targeted Delivery of Oligonucleotides with N-Acetylgalactosamine Conjugation
Hao Cui1, Xinying Zhu1, Shuyue Li1
1College of Life Science, Jiangxi Normal University, Nanchang 330022, People's Republic of China.
Abstract:
The potential therapeutic application of oligonucleotides (ONs) that selectively suppress target genes through antisense and RNA interference mechanisms has attracted great attention. The clinical applications of ONs have overcome multiple obstacles and become one of the most active areas for the development of novel therapeutics. To achieve efficient and specific cellular internalization, conjugation of a variety of functional groups to ONs has been the subject of intensive investigations over the past decade. Among them, a promising liver-targeted N-acetylgalactosamine (GalNAc) ligand has been evaluated in multiple preclinical and clinical trials for improving the cellular uptake and tissue specific delivery of ONs. GalNAc-based delivery relies on the fact that liver hepatocytes abundantly and specifically express the asialoglycoprotein receptor that binds and uptakes circulating glycoproteins via receptor-mediated endocytosis. In recent years, encouraging progress has been made in the field of GalNAc conjugates. This review aims to provide an overview of GalNAc-mediated liver-targeted delivery of small interfering RNA and antisense oligonucleotides, and the immense effort as well as recent advances in the development of GalNAc-conjugated agents are described.
Insights
Oligonucleotides (ONs) show therapeutic promise by targeting genes. N-acetylgalactosamine (GalNAc) ligands enhance ON delivery to liver cells via specific receptor interactions, improving treatment efficacy.
Area of Science:
- Biotechnology
- Molecular Biology
- Drug Delivery
Background:
- Oligonucleotides (ONs) are emerging therapeutics with potential for gene suppression via antisense and RNA interference mechanisms.
- Efficient cellular internalization and tissue-specific delivery are critical challenges for ON therapeutics.
- N-acetylgalactosamine (GalNAc) conjugation has shown significant promise for liver-targeted delivery of ONs.
Purpose of the Study:
- To provide an overview of GalNAc-mediated liver-targeted delivery strategies for small interfering RNA and antisense oligonucleotides.
- To highlight recent advances and efforts in developing GalNAc-conjugated therapeutic agents.
Main Methods:
- Review of preclinical and clinical studies on GalNAc-conjugated oligonucleotides.
- Discussion of the role of the asialoglycoprotein receptor (ASGPR) in GalNAc-mediated cellular uptake.
- Analysis of receptor-mediated endocytosis pathways for GalNAc-ON conjugates.
Main Results:
- GalNAc ligands facilitate efficient and specific uptake of ONs by liver hepatocytes.
- The asialoglycoprotein receptor (ASGPR) on hepatocytes is key to GalNAc-mediated delivery.
- Significant progress has been made in developing GalNAc-conjugated ONs for liver-targeted therapies.
Conclusions:
- GalNAc conjugation is a highly effective strategy for liver-targeted delivery of oligonucleotide therapeutics.
- This approach leverages the specific expression of ASGPR on hepatocytes for enhanced cellular uptake.
- Continued development of GalNAc-conjugated agents holds immense promise for treating liver diseases.
More Related Videos
08:46Regioselective O-Glycosylation of Nucleosides via the Temporary 2',3'-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides
Published on: July 26, 2018
08:53Synthesis, Functionalization, and Characterization of Fusogenic Porous Silicon Nanoparticles for Oligonucleotide Delivery
Published on: April 16, 2019
