Abstract
Oligonucleotide therapeutics have emerged as a third distinct platform for drug discovery within the pharmaceutical industry. Five oligonucleotide-based drugs have been approved by the US FDA and over 100 oligonucleotides drugs are currently at different stages of human trials. Several of these oligonucleotide drugs are modified using the phosphorothioate (PS) backbone modification where one of the nonbridging oxygen atoms of the phosphodiester linkage is replaced with sulfur. In this review, we summarize our knowledge on receptor-mediated uptake of PS antisense oligonucleotides (ASOs) within different cell types of the liver-a privileged organ for the discovery of oligonucleotide-based therapeutics.
Keywords:
Stabilins; asialoglycoprotein receptor; hepatocytes; sinusoidal endothelial cells.
MeSH terms
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Acetylgalactosamine / metabolism
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Animals
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Asialoglycoprotein Receptor / genetics
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Asialoglycoprotein Receptor / metabolism
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Cell Adhesion Molecules, Neuronal / genetics
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Cell Adhesion Molecules, Neuronal / metabolism
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Cell Engineering / methods
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Endocytosis*
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Endothelial Cells / cytology
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Endothelial Cells / metabolism
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Gene Transfer Techniques*
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Glycoconjugates / metabolism*
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HEK293 Cells
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Hepatocytes / cytology
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Hepatocytes / metabolism
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Humans
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Kupffer Cells / cytology
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Kupffer Cells / metabolism
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Liver / cytology
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Liver / metabolism
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Mice
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Oligonucleotides, Antisense / genetics
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Oligonucleotides, Antisense / metabolism*
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Phosphorothioate Oligonucleotides / genetics
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Phosphorothioate Oligonucleotides / metabolism*
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism*
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Scavenger Receptors, Class A / genetics
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Scavenger Receptors, Class A / metabolism
Substances
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Asialoglycoprotein Receptor
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Cell Adhesion Molecules, Neuronal
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Glycoconjugates
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Oligonucleotides, Antisense
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Phosphorothioate Oligonucleotides
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RNA, Small Interfering
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Scavenger Receptors, Class A
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Stab1 protein, mouse
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Acetylgalactosamine