Physiological Roles of Asialoglycoprotein Receptors (ASGPRs) Variants and Recent Advances in Hepatic-Targeted Delivery of Therapeutic Molecules Via ASGPRs

Author(s): Jing Hu, Jia Liu, Dongliang Yang, Mengji Lu, Jian Yin

Journal Name: Protein & Peptide Letters

Volume 21 , Issue 10 , 2014


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Abstract:

The asialoglycoprotein receptor (ASGPR) is a high-capacity C-type lectin receptor mainly expressed on mammalian hepatic cells. The physiological function of ASGPR has not been completely clarified and is thought to be specific binding and internalization of galactose (Gal) or N-acetylgalactosamine (GalNAc)-terminating glycoproteins by hepatocytes. The human ASGPR is comprised of two homologous polypeptides, H1 and H2. ASGPR H1 has two splice variants (H1a and H1b) and ASGPR H2 has three splice variants (H2a, H2b, and H2c). These variants have been discovered to exist both in human liver tissues and in human hepatoma cells. Variant H1b, which has an in-frame deletion of exon 2 resulting in the loss of the transmembrane domain and is secreted as a soluble protein, encodes functional soluble ASGPR (s- ASGPR). Based on our previous results, we proposed the possible physiological function of s-ASGPR, which is well interpreted in the Galactosyl Homeostasis Hypothesis proposed by Weigel. ASGPR is one of the most promising targets for hepatic delivery. In this review, the recent progresses of cationic polysomes and liposomes as effective non-viral delivery system via ASGPR are also presented.

Keywords: Asialoglycoprotein receptor, hepatic-targeted delivery, liposome-based delivery system, lipoplexes, polymeric delivery system, splice variant.

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Article Details

VOLUME: 21
ISSUE: 10
Year: 2014
Published on: 04 September, 2014
Page: [1025 - 1030]
Pages: 6
DOI: 10.2174/0929866521666140626102429
Price: $65

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