GalNac-siRNA conjugate delivery technology promotes the treatment of typical chronic liver diseases
Abstract
Introduction Nucleic acid-based therapeutics have become a key pillar of the 'third wave' of modern medicine, following the eras of small molecule inhibitors and antibody drugs. Their rapid progress is heavily dependent on delivery technologies, with the development of N-acetylgalactosamine (GalNAc) conjugates marking a breakthrough in targeting liver diseases. This technology has gained significant attention for its role in addressing chronic conditions like chronic hepatitis B (CHB) and nonalcoholic steatohepatitis (NASH), which are challenging to treat with conventional methods. Areas covered This review explores the origins, mechanisms, and advantages of GalNAc-siRNA delivery systems, highlighting their ability to target hepatocytes via the asialoglycoprotein receptor (ASGPR). The literature reviewed covers preclinical and clinical advancements, particularly in CHB and NASH. Key developments in stabilization chemistry and conjugation technologies are examined, emphasizing their impact on enhancing therapeutic efficacy and patient compliance. Expert opinion GalNAc-siRNA technology represents a transformative advancement in RNA interference (RNAi) therapies, addressing unmet needs in liver-targeted diseases. While significant progress has been made, challenges remain, including restricted targeting scope and scalability concerns. Continued innovation is expected to expand applications, improve delivery efficiency, and overcome limitations, establishing GalNAc-siRNA as a cor…
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Chemical modifications to the siRNA backbone, combined with hepatocyte-targeted delivery via GalNAc conjugation, reduce systemic immune recognition, thereby limiting the likelihood of clinically significant immune responses.
“Chemical modifications to the siRNA backbone, combined with hepatocyte-targeted delivery via GalNAc conjugation, reduce systemic immune recognition, thereby limiting the likelihood of clinically significant immune responses [63].”
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Tissue‐specific gene delivery approaches
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- Authors
- Qin, Z.-X., Zuo, L., Zeng, Z., Ma, R., Xie, W., Zhu, X., & Zhou, X.
- Affiliations
- Guangdong Medical College (CN)
- Nantong University (CN)
- Guangdong Medical University
- Corresponding author
- Zhu, Xiao
- Zhou, Xiaorong
- Venue
- Expert Opinion on Drug Delivery
- Publisher
- Informa UK Limited
- Published
- 2025-02-18
- Volume
- 22
- Issue
- 4
- Pages
- 455-469
- ISSN
- 1742-5247 (ISSN-L)
- 1744-7593
- OpenAlex
- W4407398597
- Cited by
- 32
- References
- 182
- Citations by year
- 2026: 20 · 2025: 12
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Drug Delivery (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (32170915 and 82172931)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- siRNA delivery, chronic hepatitis B, nonalcoholic steatohepatitis, asialoglycoprotein receptor, hepatocyte targeting, RNA interference therapy, nucleic acid therapeutics, liver-targeted drug delivery, chemical conjugation
- MeSH terms
- Acetylgalactosamine, Animals, Chronic Disease, Humans, Liver Diseases, Drug Delivery Systems, Hepatitis B, Chronic, Hepatocytes, RNA Interference, RNA, Small Interfering, Asialoglycoprotein Receptor, Non-alcoholic Fatty Liver Disease
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