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Receptor-Mediated Uptake of Phosphorothioate Antisense Oligonucleotides in Different Cell Types of the Liver

by Seth, Punit P. , Miller, Colton M. , Swayze, Eric E. , Donner, Aaron J. , Prakash, Thazha P. , Harris, Edward N. , Tanowitz, Michael

in Acetylgalactosamine - metabolism / Animals / Antisense oligonucleotides / Asialoglycoprotein Receptor - genetics / Asialoglycoprotein Receptor - metabolism / Binding sites / Biochemistry / Cell Adhesion Molecules, Neuronal - genetics / Cell Adhesion Molecules, Neuronal - metabolism / Cell Engineering - methods / Drugs / Endocytosis / Endothelial Cells - cytology / Endothelial Cells - metabolism / Extracellular matrix / Gene Transfer Techniques / Glycoconjugates - metabolism / HEK293 Cells / Hepatocytes / Hepatocytes - cytology / Hepatocytes - metabolism / Humans / Kupffer Cells - cytology / Kupffer Cells - metabolism / Ligands / Lipoproteins / Liver / Liver - cytology / Liver - metabolism / Lymphatic system / Metabolism / Mice / Oligonucleotides / Oligonucleotides, Antisense - genetics / Oligonucleotides, Antisense - metabolism / Oxygen atoms / Pharmaceutical industry / Phosphorothioate / Phosphorothioate Oligonucleotides - genetics / Phosphorothioate Oligonucleotides - metabolism / Proteins / Reviews / RNA, Small Interfering - genetics / RNA, Small Interfering - metabolism / Rodents / Scavenger Receptors, Class A - genetics / Scavenger Receptors, Class A - metabolism / Sulfur

2018

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Receptor-Mediated Uptake of Phosphorothioate Antisense Oligonucleotides in Different Cell Types of the Liver

by Seth, Punit P. , Miller, Colton M. , Swayze, Eric E. , Donner, Aaron J. , Prakash, Thazha P. , Harris, Edward N. , Tanowitz, Michael

2018

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Receptor-Mediated Uptake of Phosphorothioate Antisense Oligonucleotides in Different Cell Types of the Liver

by Seth, Punit P. , Miller, Colton M. , Swayze, Eric E. , Donner, Aaron J. , Prakash, Thazha P. , Harris, Edward N. , Tanowitz, Michael

2018

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Journal Article

Receptor-Mediated Uptake of Phosphorothioate Antisense Oligonucleotides in Different Cell Types of the Liver

Seth, Punit P.,

Miller, Colton M.,

Swayze, Eric E.,

Donner, Aaron J.,

Prakash, Thazha P.,

Harris, Edward N.,

Tanowitz, Michael

2018

Overview

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.

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Publisher

Mary Ann Liebert, Inc,SAGE Publications

Subject

Acetylgalactosamine - metabolism

/ Animals

/ Antisense oligonucleotides

/ Asialoglycoprotein Receptor - genetics

/ Asialoglycoprotein Receptor - metabolism

/ Binding sites

/ Biochemistry