Cited by 34RNA Interference and Gene DeliveryNanoparticle-Based Drug DeliveryAdvanced Drug Delivery Systems

GalNac-siRNA conjugate delivery technology promotes the treatment of typical chronic liver diseases

Qin, Zhen-Xin, Zuo, Ling, Zeng, Ziran, Ma, Rongguan, Xie, Wenyan, Zhu, Xiao, Zhou, Xiaorong·2025·Expert Opinion on Drug Delivery

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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Crossref · 10.1080/17425247.2025.2466767

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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
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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