Advancement of drugs conjugated with GalNAc in the targeted delivery to hepatocytes based on asialoglycoprotein receptor
Yafang Zhang, Hongliang Liu, Weina Zhen, Tingting Jiang, Jingxuan Cui
Abstract
The asialoglycoprotein receptor (ASGPR) is specifically expressed in hepatocytes. Sugar molecules, such as asialoglycoprotein, galactose, galactosamine, and N-acetyl galactosamine (GalNAc), have a high affinity for ASGPR. This review summarizes the structure of ASGPR, the distribution of this molecule in different cells, and the factors influencing the binding of GalNAc to ASGPR. We introduce the application of GalNAc in targeted delivery into hepatocytes by forming conjugated compounds with RNAs and small molecules, and the standard methods for synthesizing GalNAc are also briefly presented. This is to provide an overview of the current research on GalNAc and to shed light on the design of the new GalNAc. • This article presented the structure of ASGPR and elucidated how the structure affects its activity on N-acetyl galactosamine. In addition, we introduced how to improve the affinity between the conjugate and the receptor from the aspects of the length and characteristics of the linker. Taking the research content of industry giants Alnylam and Ionis Pharmaceuticals as examples, the already listed siRNA and ASO drugs were introduced, and unlisted GalNAc with different structures were also shown to provide new ideas for future research.