Preclinical and Clinical Advances of GalNAc-Decorated Nucleic Acid Therapeutics

Yuanyu Huang

doi:10.1016/j.omtn.2016.12.003

Preclinical and Clinical Advances of GalNAc-Decorated Nucleic Acid Therapeutics

Mol Ther Nucleic Acids. 2017 Mar 17:6:116-132. doi: 10.1016/j.omtn.2016.12.003. Epub 2016 Dec 10.

Author

Yuanyu Huang¹

Affiliation

¹ Advanced Research Institute for Multidisciplinary Science, Beijing Institute of Technology, Beijing 100081, China; Institute of Molecular Medicine, Peking University, Beijing 100871, China. Electronic address: yyhuang@pku.edu.cn.

Abstract

A main challenge in realizing the full potential of nucleic acid therapeutics is efficient delivery of them into targeted tissues and cells. N-acetylgalactosamine (GalNAc) is a well-defined liver-targeted moiety benefiting from its high affinity with asialoglycoprotein receptor (ASGPR). By conjugating it directly to the oligonucleotides or decorating it to a certain delivery system as a targeting moiety, GalNAc has achieved compelling successes in the development of nucleic acid therapeutics in recent years. Several oligonucleotide modalities are undergoing pivotal clinical studies, followed by a blooming pipeline in the preclinical stage. This review covers the progress of GalNAc-decorated oligonucleotide drugs, including siRNAs, anti-miRs, and ASOs, which provides a panorama for this field.

Keywords: ASGPR; ASO; GalNAc; RNAi; anti-miR; liver-targeted delivery; oligonucleotide; siRNA.

Publication types

Review